Review

Melastoma malabathricum Natural Compounds as Inhibitors of Resistant

Bacterial Development

Febria Elvy Susanti¹, Mai Efdi¹* , Syafrizayanti¹, Abdi Wira Septama²

¹Department of Chemistry, Andalas University, Padang-25163, Indonesia

²Research Center for Chemistry, Indonesian Institute of Science, Kawasan PUSPIPTEK Serpong, Tangerang

Selatan-15314, Indonesia

Abstract

Melastoma malabathricum, also known as senduduk, is a plant of the Melastomataceae family widely

found in tropical Asia. It has a long history of use as an herbal remedy in traditional Chinese medicine.

Modern research has identified various pharmacological properties of M. malabathricum, including

significant antibacterial activity, even against antibiotic-resistant bacteria. Studies have shown that

extracts from M. malabathricum contain bioactive compounds such as flavonoids, terpenoids, alkaloids,

and steroids. These studies have demonstrated that these compounds inhibit the growth of various

bacteria, including resistant strains. This antibacterial potential makes M. malabathricum very promising

for further development and application in the treatment of infections caused by resistant bacteria.

Keywords: Antibacterial activity; Melastoma malabathricum; natural compounds; pharmacology; traditional medicine

Graphical Abstract

Introduction

*

Corresponding author

Email addresses: maiefdi@sci.unand.ac.id

DOI: https://doi.org/10.22437/chp.v9i1.41114

Received January 16^th2025; Accepted April 20^th2025; Available online June 01^st2025

(https://creativecommons.org/licenses/by/4.0 )

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Chempublish Journal, 9(1) 2025, 47-64

Microorganisms, including bacteria, fungi, algae,

and protists, thrive in diverse environments,

forming complex communities [1]. Bacteria are

one of the microorganisms that can become

pathogenic if abnormal growth occurs and can

cause infection in the target host [2]. The ongoing

challenge of bacterial infections has spurred the

world's population for combating various

diseases [7].

Antibacterial resistance is a serious global health

problem.

aureus (MRSA) is one example of human

pathogenic bacteria that has developed

Methicillin-resistant

Staphylococcus

resistance to various types of antibiotics [12]. To

determine the effectiveness of an antibacterial in

inhibiting bacterial growth, Minimum Inhibitory

Concentration (MIC) testing is used [13]. MIC is

the lowest concentration of an antibacterial that

can inhibit bacterial growth [14]. An antibacterial

is considered susceptible to bacteria if it inhibits

their growth at MIC concentrations that remain

safe for the human body. Conversely, resistant

bacteria show high MIC values, indicating the

need for higher doses or even treatment failure.

An increase in MIC value over time in a bacterial

continuous

particularly from natural sources. Herbal plants

exhibit strong potential as alternative

search

for

new

treatments,

antibacterial agents [3]. Over 70,000 herbal plant

species contain bioactive compounds that can be

utilized

for

natural-based

medicine.

This

approach offers the promise of effective

treatment with potentially fewer side effects

compared to some pharmaceutical products [4].

The use of plants as natural therapeutic agents

has demonstrated a broad pharmacological

spectrum, encompassing the prevention and

treatment of various human diseases, including

cancer, respiratory disorders, diabetes, and

population indicates

the development of

antibacterial resistance [15]. According to the

World Health Organization (WHO), antibacterial

resistance has caused approximately 700,000

deaths annually and is expected to continue to

increase if there are no effective preventive

measures One of the strategies to overcome this

problem is to explore the potential of the

Melastoma malabathricum plant, as seen in Figure

1, as an alternative source of antibacterial

compounds.

cardiovascular

diseases

[5].

The

diverse

mechanisms of action of active plant compounds

explain the continued growth and reliance on

traditional medicine by a significant portion of

the global population [6]. In fact, traditional

medicine, with its wide-ranging pharmacological

effects—such as anti-inflammatory, hemostatic,

anticoagulant, antioxidant, and hepatoprotective

properties—is relied upon by over 80% of the

[b]

[a]

[d]

[c]

Figure 1. Melastoma malabathricum plant. Stem (a), root (b), flower (c), dan fruit (d). Source: personal

documentation

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F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

Melastoma malabathricum is

a

commonly

Methods

occurring plant species in Southeast Asia. The

genus Melastoma, which includes this species, is

highly diverse with a total of 22 species, 2

subspecies, and 3 varieties [8]. Various parts of

this plant, ranging from leaves and stems to

roots, have long been utilized in traditional

medicine and continue to be researched for their

therapeutic potential, including as antibacterial

agents. The content of bioactive compounds in

various parts of the plant is responsible for its

antibacterial activity [9,10]. This article aims to

This study employs a qualitative descriptie

approoach that aims to prove the antibacterial

activity and antibacterial resistance of the

senduduk plant (Melastoma malabathricum). This

review compiles references from national and

international databases published in the last 10

years (2014-2024) which include secondary

metabolite

compounds

from

Melastoma

malabathricum, using search words such as

antibacterial effectiveness test and antibacterial

resistance. The journals obtained will be

collect

published

research

on

Melastoma

evaluated

antibacterial studies and antibacterial resistance

of the senduduk plant (Melastoma

according

to

the

criteria

of

malabathricum natural compounds as inhibitors

of resistant bacteria development.

malabathricum) and will be presented in tabular

format as shown in Table 1.

Table 1. Parts of the M. malabathricum plant that showed antibacterial activity

Plant

Parts

Solvent

Water

Content

Bacteria Type

MIC Category References

-

- Bacillus subtilis

- Staphylococcus aureus

Resistent

[11]

[12]

Ethanol

Flavonoids

Tannins

Terpenoids

Flavonoids

Phenols

Susceptible

- Staphylococcus aureus

- Propionibacterium acnes

- Staphylococcus epidermidis

- Bacillus subtilis

Resistent

[17]

Terpenoids

- Escherichia coli

- Bacillus cereus

- Staphylococcus aureus

- Proteus mirabilis

- Staphylococcus aureus

- Escherichia coli

- Bacillus cereus

- Salmonella typhi

- Escherichia coli

Ethanol

-

Resistent

[18]

[19]

Leaves

Flavonoids

Saponins

Tannins

Susceptible

- Staphylococcus aureus

Alkaloids

Terpenoids

Lipids

Methanol

- Bacillus subtilis

- Escherichia coli

- Pseudomonas aeruginosa

- Staphylococcus aureus

- Escherichia coli

Resistent

[20]

[21]

Ethyl

acetate

Triterpenoid

Saponins

Flavonoids

Steroids

- Staphylococcus aureus

Tannins

Ethanol

Flavonoids

Phenolics

- Streptococcus pyogenes

- Klebsiella pneumoniae

Susceptible

[22]

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F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

Plant

Parts

Solvent

Content

Tannins

Bacteria Type

MIC Category References

Terpenoids

Ethanol

Alkaloids

Flavonoids

Tannins

- Propionibacterium acnes

Resistent

[23]

Steroids

Triterpenoid

Carbohydrate

Saponins

Stems

Roots

Acetone

Ethanol

Triterpenoid

Lipids

Saponins

Flavonoids

Triterpenoid

Tannins

- Streptococcus mutans

- Escherichia coli

Susceptible

Resistent

[24]

[25]

Ethanol

-

- Shigella dysenteriae

Susceptible

Resisten

[26]

[27]

Methanol:

water

Flavonoid

Steroids

- Staphylococcus aureus

- Bacillus cereus

Terpenoids

Phenolics

Lipids

Ethanol

Methanol

Flavonoids

- Staphylococcus aureus

- Listeria monocytogenes

- Staphylococcus aureus

- Escherichia coli

Resistent

[28]

[29]

Flowers

- Salmonella typhimurium

Methanol

Tannins

- Listeria monocytogenes

- Staphylococcus aureus

Resistent

Intermediate

[30]

Steroids

Phenols

Flavonoids

Results and Discussion

Senduduk's bioactive

malabathricum plants showed that the presence

of secondary metabolites such as alkaloids,

flavonoids, carbohydrates, saponins, and tannins

could show an excellent potential to develop as

an alternative treatment agent, including

treatment against resistant bacteria [12]. The

content of bioactive compounds in senduduk

plants, namely saponins, tannins, flavonoids,

triterpenoids, and steroids, can potentially

control the development and growth of bacteria

[31]. Saponins can increase the permeability of

bacterial cell membranes and cause the release

of intracellular compounds [32]. In addition,

compounds

and

antibacterial potential.

Melastoma

malabathricum,

well-known

as

senduduk, is widely distributed in various parts

of Southeast Asia. Apart from being an

ornamental plant, senduduk also has potential as

a source of natural antibacterial compounds due

to its bioactive compounds. Various plant parts,

including leaves, stems, flowers, and roots,

contain

Phytochemical

bioactive

compounds

[31].

screening

of Melastoma

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Chempublish Journal, 9(1) 2025, 47-64

flavonoids in senduduk can form complexes with

extracellular proteins, potentially damaging

bacterial cell membranes [33].

can interact with phospholipids in bacterial cell

membranes. The resulting interaction can cause

morphological disturbances in bacterial cells and

ultimately can cause damage to the bacterial cell

wall gradually [37]. Compounds found in

senduduk may show significant potential in

treating various diseases, including antitumor,

anti-inflammatory, antiviral, and antibacterial.

These findings support the use of senduduk in

traditional medicine practices [38].

According to research by Faradiba et al. (2016)

[34], senduduk contains flavonoids rich in phenol

compounds that can cause protein denaturation,

damage cell membranes, and damage protein

structures. These flavonoids have the potential to

act as antibacterial substances with the

mechanism of disrupting bacterial metabolism,

damaging cell walls, disrupting protein synthesis,

and inhibiting the performance of bacterial

enzymes [35]. Therefore, flavonoids contained in

senduduk can reduce bacterial proliferation and

support the reduction of the number of disease-

causing bacteria [36]. Another content contained

in this plant is steroids, which are permeable and

Secondary metabolites are produced through

complex biosynthetic pathways, starting from

primary

metabolites

(fundamental

organic

matter) such as carbohydrates, amino acids, and

isoprenoid units. Plants rich in these primary

metabolites have the potential to produce a

variety of unique secondary metabolites [45].

Table 2. Senduduk compounds that show pharmacological activity

Secondary

Metabolites

Alkaloids

Activities

References

Antimicrobial, anti-inflammatory

[39]

[40]

Saponin

Anti-carcinogenic, antimicrobial, immunomodulatory

properties, anti-inflammatory, influence on blood

pressure

Tanin

Terpenoids

Antimicrobial, anti-inflammatory, antioxidant,

[41]

[42]

Anti-carcinogenic,

antimicrobial,

anti-inflammatory,

cholesterol lowering effect

Steroids

Anticancer, anti-inflammatory, antibacterial, antifungal,

antiviral

Antioxidant, anti-alzheimer, antimicrobial, anticancer,

[43]

[44]

Flavonoids

anti-inflammatory, antidiabetic

Secondary metabolites have extensive potential

in pharmacology. As shown in Table 2, these

compounds can function as antioxidants,

antimicrobials, anticancers, anticoagulants, and

inhibit carcinogenic effects, among others. In

addition, secondary metabolites can also utilize

membrane structure. Flavonoids, for example,

are known to have antibacterial activity [47]. An

in-depth understanding of these interaction

mechanisms may pave the way for developing

more effective and selective drugs and reduce

the problem of antibacterial resistance [48].

as

environmentally

friendly

pest

control

How Natural Compounds in Senduduk Can

Inhibit the Growth or Kill Bacteria

antiagents [45].

Figure 2 shows the interaction of natural

compounds such as flavonoids, terpenoids,

alkaloids, and steroids with bacterial cell

membranes [46]. These compounds can interact

with various membrane components, including

proteins, lipids, and peptidoglycans. These

interactions can alter membrane permeability,

disrupt protein function, or even damage

Bacteria can resist antibacterials through various

mechanisms, one of which is by modifying their

cellular structure. For example, bacteria can alter

their

ribosomes

through

the

action

of

methyltransferase enzymes that are affected by

the antibacterial itself [45]. Prolonged antibiotic

use contributes to resistance, necessitating the

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F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

search for alternative treatments such as natural

side effects, more affordable costs, and easier

distribution [48].

compound.

Natural

medicines

like

those

produced by senduduk generally have minimal

Figure 2. Natural compounds interaction with bacteria cell membrane [46]

Plants

produce

primary

and

secondary

to test the antibacterial effect in humans. The

mechanism of action of flavonoids is different

from that of conventional drugs [53]. Several

studies have shown that flavonoids can disrupt

bacterial cell membrane function, inhibit growth

and metabolism, damage cell walls, inhibit

protein synthesis, and inactivate enzymes

important for bacteria [35,54].

metabolites for their survival [49]. Secondary

metabolites, such as terpenoids, alkaloids,

polyketides, and sulfur-containing compounds,

have potential as natural antibacterial agents.

These compounds can inhibit the growth or kill

pathogenic

mechanisms,

bacteria

such as

cell

through

inhibiting

various

protein

synthesis,

damaging

membranes,

or

Based on the antibacterial mechanism shown in

Figure 3, flavonoids have great potential as new

antibacterial agents. These compounds can

inhibit bacterial growth by damaging cell

membranes, inhibiting nucleic acid synthesis,

and disrupting biofilm formation. This potential

inhibiting essential enzymes for bacteria [49].

The potential of biological compounds with such

bioactivity is very promising to be further

developed and researched as an alternative

treatment against pathogens [50].

Effects of Flavonoids.

makes flavonoids

a

promising candidate.

However, further research is needed to address

the growing problem of antibacterial resistance

to optimize their biological activity and evaluate

the safety of their use [55].

Flavonoids are secondary metabolites commonly

found in various plants. These compounds not

only play a role in providing attractive colors to

flowers and fruits to attract insects for pollination

[51], but also have important functions as

antibacterials. Flavonoids help plants fight

pathogen infections by enhancing immunity and

through complex biosynthesis processes [52].

Figure 3 shows the various mechanisms by which

flavonoid compounds can inhibit bacterial

growth. Some of the main mechanisms include

disruption of the cell membrane (1), inhibition of

nucleic acid synthesis through dihydrofolate

reductase, helicase, and gyrase enzymes (2a-c),

inhibition of biofilm formation (3&4), disruption

Considering the potential of flavonoids in fighting

pathogens, various studies have been conducted

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Chempublish Journal, 9(1) 2025, 47-64

of macromolecular synthesis (6, 7a-b), and

inhibition of the electron transport chain through

NADH-cytochrome c reductase and ATP synthase

complexes [8,9,56].

activity. Flavonoids generally consist of two

benzene rings connected by three carbon atoms

(Figure 3). The position and type of functional

groups on this basic skeleton significantly affect

flavonoids' physicochemical properties and

biological activity, including their ability to

interact with various biomolecular targets [57].

The structure of flavonoid compounds plays an

important role in determining antibacterial

Figure 3. Antibacterial mechanism of flavonoids compounds [56]

groups can inhibit the formation of hydrogen

bonds, which play an important role in the

binding of flavonoids to bacterial targets. This

reduction in hydrogen bond potential can

decrease binding affinity, resulting in a decrease

in

antibacterial

activity

[59,60].

Besides

hydroxylation and methoxylation, prenylation is

an important structural modification that can

enhance the antibacterial activity of flavonoid

compounds. The addition of isoprenyl groups to

flavonoid structures, especially the C-5, C-7, and

C-4′ positions, often results in compounds with

strong antibacterial activity, including against

Figure 4. Basic structure of flavonoids compound

Structural modification of flavonoids can affect

their antibacterial activity (Figure 4). Adding

hydroxyl groups (-OH) at positions C-5, C-7, C-3′,

and C-4′ increases the antibacterial potential. The

increase is due to stronger interactions with

bacterial proteins and more effective disruption

of cell membrane integrity [58]. In contrast,

substituting hydroxyl groups with methoxy

groups (-OCH₃) at positions C-3′ and C-5

decreases antibacterial activity. The decrease

suggests that the presence and position of

resistant

Staphylococcus

prenylation and hydroxylation at specific

positions can produce synergistic effects,

increasing the potential of flavonoids as effective

antimicrobial agents [61].

pathogenic

bacteria

(MRSA).

such

Combining

as

aureus

Some pure compounds successfully isolated

from senduduk plants are kaempferol, quercetin

[62], and rutin [63]. Kaempferol, a flavonoid with

a distinctive structure characterized by hydroxyl

functional

groups

strongly

influence

the

interaction between flavonoids and bacterial

target molecules. The presence of methoxy

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F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

groups at positions 5, 7, 3, and 4', has shown

significant antibacterial activity by inhibiting

FabG and enoyl-acyl carrier protein reductase

enzymes. This mechanism interferes with the

biosynthesis of fatty acids essential for bacterial

cell membrane integrity and biofilm formation

[64]. In vitro studies reported IC₅₀values of

kaempferol against Staphylococcus aureus and

Escherichia coli of 3.125 mg/mL and 6.25 mg/mL,

respectively, indicating potential as a potent

antibacterial agent [65]. The IC₅₀value is the

lowest compound concentration required to

inhibit 50% bacterial growth [66]. This parameter

is crucial in evaluating antibacterial activity for

new drug development. The lower the IC₅₀value,

the stronger the compound's ability to inhibit

bacterial growth, allowing for more optimal

dosing and minimizing the risk of side effects

[67].

increased

significantly

when

rutin

was

formulated into nanocrystals, reducing the IC₅₀to

6.85

μg/mL.

This

indicated

rutin increased

that

the

its

nanoformulation

of

effectiveness in inhibiting the urease enzyme,

which is a key factor in the survival and

pathogenicity of Helicobacter pylori [73].

Effects of Terpenoids.

Terpenoids are natural compounds that play

important roles in various biological processes in

plants. The lipophilic nature of terpenoids allows

these compounds to penetrate bacterial cell

membranes mostly composed of lipids [74].

Besides functioning as photosynthetic pigments

and growth hormones, terpenoids are also

known as effective antibacterial agents [75]. The

lipophilic nature of terpenoids allows these

compounds

to

penetrate

bacterial

cell

membranes mostly composed of lipids [76][77].

Quercetin, another flavonoid similar in structure

to kaempferol, also has broad antibacterial

activity. Its main mechanism of action is inhibiting

the enzyme D-alanine: D-alanine ligase, which

inhibits the synthesis of peptidoglycan, an

essential component of bacterial cell walls [68]. In

a study by Zhang et al. (2022) [69], quercetin

showed potential as a potent inhibitor of the

OXA-48 beta-lactamase enzyme with IC₅₀values

between 0.042 mg/mL to 0.413 mg/mL. OXA-48

enzyme plays an important role in antibacterial

resistance. These results indicate that quercetin

can restore the effectiveness of antibacterials

such as piperacillin and imipenem against

resistant Escherichia coli strains. In addition to its

After penetrating the membrane, terpenoids can

interfere with various bacterial cell functions.

One of the main mechanisms is damage to the

integrity of the cell membrane. By forming pores

in the membrane, terpenoids cause leakage of

important ions and molecules and disrupt the

concentration gradient necessary for cell

survival. In addition, terpenoids can also inhibit

the production of ATP, the main energy source of

cells,

thereby

disrupting

various

cellular

metabolic processes [11,78].

One of the significant problems in treating

infections is the emergence of resistant bacteria.

antibacterial

effects,

quercetin

has

anti-

Resistant

bacteria

often

have

defense

inflammatory and antioxidant properties that

can potentially accelerate the wound healing

process [70]. Furthermore, rutin is a flavonol

glycoside derived from quercetin with an added

sugar group. Rutin has potent antioxidant activity

and shows potential as an antibacterial and

antibiofilm agent [71]. Its mechanism of action

includes inhibition of biofilm formation, which is

a collection of bacterial cells encased in an

extracellular polymer matrix. Biofilms provide

protection for bacteria against antibiotics. By

inhibiting biofilm formation, rutin can increase

the effectiveness of antibiotics [72]. Rutin

showed an IC₅₀of 97.8 μg/mL for inhibiting the

Helicobacter pylori urease enzyme. The value

mechanisms that allow them to evade the effects

of antibacterials, such as changes in the structure

of the cell membrane or drug-target enzymes.

Uniquely, terpenoids can overcome these

resistance

mechanisms

differently

[79].

Terpenoids have multiple target molecules inside

bacterial cells, making it difficult for bacteria to

develop resistance to all targets at once [80-82].

Further antibacterial mechanisms of terpenoid

compounds can be seen in Figure 4.

Figure 5 visually presents a comprehensive

picture of the diversity of terpenoid molecular

targets in bacterial cells. These compounds are

shown to be able to intervene in various essential

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Chempublish Journal, 9(1) 2025, 47-64

processes in bacterial cells, thus inhibiting their

growth and survival. The main mechanisms

depicted include: (1) cell membrane disruption;

terpenoids can damage the integrity of bacterial

cell membranes, causing leakage of vital cellular

components and disruption of cell homeostasis

[83]. (2) modulation of efflux pumps; these

compounds can inhibit bacterial efflux pumps

that play a role in removing antibacterials from

the cell, thereby increasing the effectiveness of

concomitantly administered antibacterials [84].

(3) inhibition of oxygen uptake; by interfering

with the process of cellular respiration,

terpenoids limit the production of energy that

bacteria need to survive [85]. (4) disruption of

interfere with the electron transport chain,

thereby inhibiting the production of ATP as the

cell's primary energy source [86]. (5) inhibition of

virulence factors; some terpenoids are able to

inhibit the production of bacterial virulence

factors, which play an important role in the

infection process [87]. (6) reduction of cell

adhesion ability; by inhibiting the ability of

bacteria to adhere to surfaces, terpenoids can

prevent biofilm formation and the spread of

infection [88]. Finally, (7) suppression of biofilm

formation; terpenoids can inhibit the formation

of bacterial biofilms, which are communities of

bacterial cells embedded in the extracellular

matrix and challenging to eradicate [89].

oxidative

phosphorylation;

terpenoids

can

Figure 5. Antibacterial mechanism of terpenoids compound [75]

The structure of terpenoid compounds is very

diverse due to the various bonding possibilities

(single, double), ring formation (cyclization), and

the addition of different functional groups. It is

this structural variation that gives terpenoids

their unique physical and chemical properties, as

well as a wide range of biological activities [90].

The basic building unit of all terpenoids is

isoprene, a molecule with five carbon atoms

(Figure 6).

The presence of a hydroxyl group (-OH) on the

terpenoid structure often enhances its

antibacterial activity compared to hydrocarbon

compounds. This can be seen in the example of

eugenol and terpineol compounds. These two

compounds have the ability to kill bacteria

quickly because they can damage the bacterial

cell membrane [91].

α-Amyrin,

a

purified terpenoid successfully

isolated from the senduduk plant [92], shows

broad pharmacological potential, including anti-

inflammatory and antioxidant properties. In the

rat ear edema test, α-amyrin was shown to be

very effective in inhibiting inflammation with an

Figure 6. Structure of the isoprene unit

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F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

IC₅₀value of 0.0469 mg/mL [93]. α-Amyrin is a

major precursor in forming ursolic acid, a

compound with high commercial value thanks to

its various health benefits. The enzyme α-amyrin

synthase catalyzes the conversion of (3S)-2,3-

oxidosqualene to α-amyrin in its biosynthesis

process [94, 95].

pharmacological effects such as analgesic,

antipyretic, and anticancer, as well as significant

potential toxicity [96][97].

Alkaloids have diverse antibacterial activities.

These compounds can inhibit bacterial growth

and replication by disrupting the synthesis of

nucleic acids and proteins that are essential for

bacterial cells. Furthermore, alkaloids can also

Effects of Alkaloids.

damage

the

integrity

of

bacterial

cell

Alkaloids, as secondary metabolites rich in

nitrogen and alkaline in nature, are commonly

extracted from plants but can also be found in

animals and microorganisms. The structural

diversity of alkaloids confers their broad

biological activities, encompassing favorable

membranes, causing leakage of vital cellular

components and ultimately cell death (Figure 7)

[98].

Figure 7. Antibacterial mechanism of alkaloids compound [98]

Figure 6 shows some of the ways alkaloids work

to inhibit growth and kill bacteria. Alkaloids can

interfere with various important processes in

bacterial cells. First, alkaloids can inhibit bacterial

cell division so the bacteria cannot multiply [99].

Secondly, alkaloids can also interfere with

bacterial protein synthesis by inhibiting the

transcription and translation processes [98]. This

process is essential for bacteria to produce the

proteins needed to survive. Besides, alkaloids

can also damage bacterial cell membranes [100].

By damaging the cell membrane, alkaloids cause

leakage of cell contents and eventual bacterial

cell death. Another possible mechanism is the

inhibition of important enzymes in bacteria, such

as enzymes involved in energy metabolism [101].

Lastly, alkaloids can also affect efflux pumps in

bacteria [102]. Efflux pumps are proteins that

pump out foreign substances from inside

bacterial cells. By inhibiting efflux pumps,

alkaloids allow harmful substances, including

themselves, to remain inside the bacterial cell

and cause damage [103]. The ability of alkaloids

to interfere with various cellular processes in

bacteria makes them attractive compounds to be

developed as alternative antibacterials.

The mechanism of action of alkaloids is very

diverse and is influenced by their complex

chemical structure. Differences in functional

groups, such as methylenedioxy (-O-CH₂-O-) and

methoxyl (-OCH₃), on the benzene ring structure

can significantly affect their biological activity. A

study in 2009 showed that methylenedioxy

groups generally enhanced antibacterial activity

more than methoxyl groups [104].

Auranamide and patriscabratine are new

alkaloids successfully isolated from senduduk

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Chempublish Journal, 9(1) 2025, 47-64

plants [92]. Both have unique structures that

correlate with their antibacterial activity. The

amide groups in both compounds are thought to

play a role in forming hydrogen bonds with

bacterial protein targets, thus inhibiting essential

protein functions. The aromatic ring provides

structural rigidity and interacts hydrophobically

with the cell membrane, disrupting its integrity.

The hydroxyl group increases solubility, while the

methoxy group on patriscabratine likely affects

membrane permeability. Auranamide showed

no toxicity to cells up to a concentration of 5.066

mg/mL and dose-dependently inhibited the

production of nitric oxide and proinflammatory

cytokines in mouse macrophages. In addition,

this compound activated the NRF2 pathway,

action may involve interference with bacterial

cellular processes, such as pigmentation. Even at

low concentrations, these compounds are

already quite effective. Moreover, to antibacterial

activity, steroids also have important roles in

various biological processes, such as hormones

that

regulate

growth,

development,

and

metabolism. Cholesterol, a type of steroid, is an

important component of cell membranes. Some

other steroids, such as vitamin D, play a role in

calcium absorption [111].

Perhydrophenanthrene

which plays

a

role

in cellular

defense

mechanisms against oxidative stress [105].

Patriscabratine also exhibits anti-inflammatory

activity and activates the NRF2 pathway. The

similarity in structure to aurantiamide acetate, a

cathepsin

L

inhibitor,

suggests

that

Figure 8. Basic structure of steroid compound

patriscabratine might also inhibit the enzyme.

The IC₅₀value of patriscabratine is thought to be

similar to that of aurantiamide acetate, although

the exact value is yet to be determined [106].

Steroid compounds can fight bacteria in various

ways, such as damaging the bacterial cell

membrane, disrupting activities within the

bacterial cell, and stimulating the immune

system [112]. For example, the linoleic acid ester

17α-hydroxyprogesterone damages bacterial

membranes [113]. Besides damaging bacterial

cell membranes through mechanisms such as

membrane destabilization and cell lysis, steroid

compounds can also inhibit protein synthesis,

damage DNA, or modulate bacterial cellular

Effects of Steroids.

Steroids, secondary metabolites of plant and

animal origin, have been widely used in medicine.

These compounds have broad pharmacological

potential and are often used as the basis for

developing drugs for various diseases [107].

Recent research has shown that bacteria such as

actinobacteria and proteobacteria can degrade

steroids

[108].

This

potential

opens

up

regulatory

systems

[112][114][115].

Some

opportunities for developing new steroid

compounds that are more effective in fighting

infections. Several in vitro studies have also

demonstrated the effectiveness of steroid

steroid compounds can even stimulate the host

immune system to fight infection through

increased activity of defense enzymes such as

superoxide

dismutase

and

catalase

and

compounds

in

inhibiting

the

growth

of

increased synthesis of endogenous antibacterial

compounds [116]. Recent studies have shown

that specific steroid compounds, such as the

linoleic acid ester 17α-hydroxyprogesterone,

interact with bacterial membrane components

such as phosphatidylethanolamine, leading to

membrane destabilization and bacterial cell lysis.

In addition, steroid derivatives such as androst-4-

ene compounds have been shown to enhance

microorganisms and reducing infections.[109].

The basic structure of steroids consists of a

perhydrophenanthrene core (Figure 8). This core

can be modified with various functional groups,

including nitrogen, to increase its effectiveness

against bacteria. Nitrogen-containing steroids,

such as azasteroids, often show strong

antibacterial activity, especially against gram-

positive bacteria [110]. Their mechanism of

57

F.E. Susanti et al.

Chempublish Journal, 9(1) 2025, 47-64

host defenses by increasing defense enzyme

activity and salicylate synthase content [117]. The

unique mechanism of action of antibacterial

steroids, which often involves disrupting the

bacterial cell membrane, provides hope in

overcoming the growing problem of antibacterial

resistance. However, further research is needed

only valuable in preserving traditional medicine,

but also opens up new opportunities in the

development

of

natural

pharmaceuticals,

particularly in combating drug-resistant bacteria.

Further research should focus on isolating and

characterizing the specific bioactive compounds

responsible for its antibacterial effects, as well as

exploring its efficacy in clinical trials. This will help

to fully realize the therapeutic potential of M.

to

comprehensively

compounds' mechanism of action, safety, and

understand

these

clinical efficacy.

malabathricum

development of novel antibacterial agents.

and

contribute

to

the

Senduduk plants contain various types of

steroids, such as sitosterols, which have strong

antibacterial activity. Although the amount is

relatively small, these steroids contribute

significantly to the antibacterial properties of

senduduk plants. Research shows that sterols

comprise about 5.77% of the total compounds in

its leaf extract [118]. Antibacterial tests showed

that specific sterols, especially fucosterol and

epicoprostanol, have potent antibacterial activity

against gram-negative bacteria with IC₅₀values

ranging from 0,2663 to 0,4258 mg/mL [119].

Furthermore, the study showed that sitosterol,

isolated from the hydroid Aglaophenia cupressina

Lamouroux, exhibited significant antibacterial

properties, especially against Staphylococcus

aureus and Shigella sp., with the most effective

concentration of 30 ppm producing the largest

zone of inhibition for both bacteria. This study

shows that sitosterol has a bacteriostatic effect,

i.e., it inhibits the growth of Staphylococcus aureus

and Shigella sp. without killing the bacteria,

Acknowledgement

This research supported by the Directorate of

Talent Management of the National Research

and Innovation Agency (BRIN) for the Degree by

Research (DBR) program.

Author Contributions

Conceptualization, Methodology, dan Validation,

M.E., F.E.S., S., A.W.S.; Writing – Original Draft

Preparation, F.E.S.; Writing – Review & Editing,

M.E., F.E.S., S., A.W.S.

Conflict of Interest

The authors declare no conflict of interest

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