ORGANO SULFUR COMPOUNDS AS ANTIMICROBIAL AGENT
Moumik Mandal1*, Swagata Bakshi1, Pratibha Bhowmick1, Mithun Bhowmick1
Bengal College of Pharmaceutical Sciences and Research Durgapur, West Bengal
Email id: moumikmandal283@gmail.com
Inatconph-24/236/PP-042
ABSTRACT
Organosulfur compounds act as antimicrobials, anticancers, immunomodulators, etc. obtained from Allium sativum. Besides Allium sativum, it is also found in Allium cepa. These compounds contain sulfur, which is an essential component for the formation of
essential secondary metabolites. The sulfur-containing components in allium are derived from γ-glutamyl-S-alkenyl-L-cysteins and S-alkenyl-L-cystein sulfoxides. These are therapeutically active compounds of onion and garlic. The organosulfur compounds found
in garlic show a broad range of antibacterial properties, such as bactericidal, antibiofilm, antitoxin, and bacteriocidal activity against a wide range of gram-positive and gram-negative bacteria, including multi-drug-resistant strains. The reactive organosulfur
compounds form disulfide bonds with free sulfhydryl groups of enzymes and compromise the integrity of the bacterial cell membrane. Organosulfur compounds also bind to essential enzymes like cysteine proteases and DNA gyrase to prevent DNA replication. An
important organosulfur compound, allicin, forms a covalent bond with the active site of the cysteine residue of the protease enzyme. It also interacts with the thiol group of Cystein and inhibits enzymatic activity. Organosulfur compounds can be useful
antimicrobial agents, as they have been shown to have less toxicity than other conventional antimicrobials. In this study, the potential of organosulfur compounds as antimicrobial agents and their properties are discussed. Many preclinical and clinical studies
support that organosulfur compounds are very effective as antimicrobial agents.
Keywords- antimicrobial, cysteine protease, dna gyrase, allicin, cysteine residue, organosulfur compounds
INTRODUCTION
Organosulfur compounds are obtained from natural origin like
Allium cepa, Allium sativum . It contain sulfur, essential for
formation of secondary metabolites. These compounds are
derived from γ-glutamyl-S-alkenyl-L-cysteine and S-alkenyl-Lcysteine sulfoxides. This compounds are broad spectrum
antibacterial agent. I also effective against multidrug resistant
strains. Allicin, an organosulfur compound, forms covalent bond
with the active site of cysteine residue and protease enzyme.
Organosulfur compound interact with thiol group of cysteine to
inhibit enzymatic activity.
ORGANOSULFUR COMPOUNDS
ORGANOSULFUR COMPOUND AND ITS SOURCES
PHARMACOLOGICAL ACTIVITY
❖ Allicin
Antibacterial, Antifungal and Antiviral
❖ Diallyl Sulfide
Antibacterial, Antiangiogenic, Anticancer, Anticoagulant
❖ Sulforaphane
Anticancer, Anti-inflammatory, Antioxidant, Antidiabetic, Cardioprotective
❖ Diallyl trisulfide
Anticancer, Anti-inflammatory, Antioxidant, Antiviral, Antifungal
❖ S-Allylmercaptocysteine Anti-inflammatory, Antioxidant, Anticancer, Hepatoprotective, Neurotopic
Allicin
Garlic, Elephant garlic, Scallion, Shallots
Diallyl Sulfide
Garlic, Onion, Leeks, Chives, Fermented Food
Sulforaphane
Broccoli, Cauliflower, Kale, Cabbage, Brussels Sprout
Diallyl Trisulfide
Garlic, Elephant garlic, Onion, Shallot, Garlic oil
S-Allylmercaptocysteine Garlic, Garlic extract supplement, Aged Garlic Extract,
Fermented Garlic
Mechanism of action for Organosulfur Compounds
Molecular Docking Software
for Organosulfur Compounds
Mechanism of Action of Sulforaphen
Mechanism of Action Diallyl Sulfide
Mechanism of Action of Allicin
Micro-organisms Affected by Organosulfur Compounds
Organosulfur
Compounds
Affected Bacteria
Allicin
E. coli,
Candida albicans, HIV 1 HSV 1
C
difficile, Aspergillus nigur, Influenza A virus ,
Salmonella enterica Sacharomyses
Rotavirus
cerevisiae
Diallyl Sulfide
Sulforaphane
E.
coli,
Staphylococcus
aureus,
Bacillus
subtilis,
Pseudomonus
aeruginosa
Affected Fungus
Affected Virus
Main antimicrobial effect of allicin is due to
its chemical reaction with thiol groups of
various
enzymes,
e.g.
alcohol
dehydrogenase, thioredoxin reductase and
RNA polymerase which can effect essebtial
metabolism of cysteine proteinase activity
involved in the virulence of E. histolytica.
Candida albicans, InfluenzaA, HIV
Aspergillus flavus, 1
Fusarium
oxysporum
The protein leakage was enhanced at acidic pH.
Scanning Electron Microscopy of B. cereus treated
with DAS showed deformation in the cell membrane.
Thus the data indicate DAS exerts its antibacterial
activity by compromising membrane integrity of B
cereus. The study demonstrate Diallyl Sulfide could
be used to control cereus infection. The finding
indicates that Das have a membrane altering activity,
suggesting that development of resistance to this
mechanism is less likely and the compound could be
novel antibacterial or a good adjuvant for
antibiotics.
Mechanism of action of Sulforaphen action
includes the affecting of membrane
integrity and enzyme involved in the redox
balance and metabolism which leads to
bacteria death.
❖ Glide
❖ GOLD
❖ FlexX
❖ Molecular Operating
Environment
Helicobacter pylori, Candida albicans, HPV, HBV
E coli, Salmonella Aspergillus niger
enterica,
Listeria
monocytogenes
Bacillus cereus bacteria
Diallyl Trisulfide MRSA, E coli, Candida albicans, Influenza A, HIVBacilus
subtitis, Aspergillus flavus 1
Pseudomonus
aueriginosa
SE. coli, S. Aureus, Candida albicans, HIV 1, HSV 1
Allylmercaptocys Salmonella enterica Aspergillus niger
teine
Listeria
monocytogens
❖ AutoDock
Structures of Organosulfur compounds
Bacillus cereus cell membrane
Entamiba hystolytica
Diallyl sulfide
Allicin
Molecular Docking of organosulfur compounds
▪ Allicin
▪ Diallyl sulfide
Diallyl trisulfide
➢ Bacterial Enzymes - βlactamase, DNA Gyrase
➢ Viral Proteins - HIV-1
Protease,
HSV
1
Thymidine Kinase
➢ Human Enzymes – ACE,
COX2
✓ Binding to active site to
inhibit enzymatic activity
✓ Hydrogen
Bonding,
Hydrophobic interactions
➢ Bacterial Quorum sensing
receptor – LuxR
➢ Viral Proteins – Influenza A
virus NS1
➢ Human Enzyme – CYP2E1
✓ Interaction
with
Hydrophobic pocket and
disruption protein function
✓ H bonding, Hydrophobic
and S based interaction
▪ Sulforaphane
➢ Bacterial two components
system – Histidine Kinase
➢ Viral Protein – HPV E6
➢ Human
Transcription
factors
▪ Diallyl Trisulfide
Sulforaphane
✓ Binding to allosteric site to
modulate Protein activity
✓ π-π stacking, H bonding and
S based interaction
➢ Bacterial
Membrane
Proteins – Efflux Pumps
➢ Viral Proteins – HIV1gp41
➢ Human Enzyme - GST
✓ Interaction with Hydrophobic
region and disruption cell
membrane rigidity
✓ H
bonding,
Hydrophobic
interaction and π-π staking.
➢ Bacterial
Enzyme
–
Thioredoxin Reductase
➢ Viral Proteins – HSV-1 TK
➢ Human Enzymes - GST
✓ Binding active site inhibiting
enzyme activity
✓ H bonding , Hydrophobic and
Sulfur based interaction
▪ S-Allylmarcaptocysteine
Conclusion
The antimicrobial activity of organosulfur compounds particularly through their inhibitory effects on DNA
Gyrase, HIV 1 Proteases Bacterial quorum sensing etc. It highlight interaction between traditional
knowledge and modern scientific research. These compounds not only shows effectivity against microbes but
also show importance implanting traditional knowledge in modern scientific methodologies.
Acknowledgement
The author would I like to convey his deepest
gratitude to his guide Ms. Swagata Bakshi &
other members of Bengal college of
Pharmaceutical sciences and research for
making this poster in present form.
REFFERENCES
1. Singh et al. (2022). Molecular docking studies of allicin. Journal of Molecular Graphics and Modelling, 111, 10,81,35
2. Lee et al. (2021). Diallyl Sulfide: Molecular Docking and antimicrobial activity. Bioorganic chemistry, 117, 105-456
3. Kumar et al. (2022). Sulforaphane: Molecular Docking and anticancer activity. Journal of molecular recognition, 35(2). E29,22
4. Chen et al. (2021). Diallyltrisulfide: Molecular Docking and Anti-inflammatory activity. European Journal of Pharmacology, 906, 17,45,32
5. Wang et al. (2022). S-allylmercaptocysteine: Molecular Docking and antioxidant activity. Biochemical and Biophysical Research Communications, 594, 4450
6. Li at al. (2022). Antibacterial activity of Allicin against MRSA and E. coli, Journal of Applied Microbiology, 132(2), 531-539
7. Kim et al. (2021). Diallyl sulfide exhibit antimicrobial activity against P. aeruginosa. Biochemical and Biophysical Research Communications, 564, 133-139
8. Lee et al. (2020). Sulforaphane inhibits biofilm formation in E coli and P. aeruginosa. Journal of Microbiology and Biotechnology, 30(10), 1431-1438
9. Choi et al. (2022). Antiviral activity of Diallylsulfide in SARS-COV 2. Virology, 573, 63-71
10.Wang et al. (2021). Sulforaphane inhibits HPV E6 expression. Journal of Medicinal food, 24(10), 1039-1046
S Allyl mercaptocysteine
Research Finding
1. Singh et al 2022 shows that Allicin Docked to β lactamase, DNA Gyrase, HIV 1
Protease showing inhibitory activity. Inhibition of β lactamase leads to increase
effectivity against resistant bacteria. It prevent substrate binding. In case DNA
Gyrase Allicin bind to GyrA subunit prevent ATP Hydrolysis which causes
disruption of DNA replication. In case of HIV 1 Protease it binds active site to
prevent substrate binding which further prevent DNA replication.
2. Lee et al 2021 shows that Diallyl sulfide bound to bacterial quorum sensing
receptors, viral NS1 Protein and Human CYP2E1. Diallyl Sulfide bind to LuxR of
QSR preventing autoinducer binding and subsequent gene expression leads to
disruption of bacterial communication. It bind to NS 1 protein preventing
interaction with viral RNA and host cell protein and inhibit viral replication. It
This
bind to active site of CYP2E1 preventing substrate binding.
Photo
by
3. Kumar et al 2022 shows that Sulforaphane interact with bacterialUnkno
Histidine kinase,
wn
Viral HPVE6 and Human Nrf2. Sulforaphane binds to HK’s Author
ATP binding site
is
prevents autophosphorylation leads ton inhibition of HK license
and two
dactivity
under
CC BYcomponent system. It attenuate Bacterial virulece, biofilm formation
and antibiotic
SA
resistance. SFN binds to HPVE6 preventing p53 binding and degradation, Leads to
induction apoptosis in HPV positive cancer cell inhibiting tumor growth. SFN binds
to Keap 1 releasing nrf2 alowing nuclear translocation protect against oxidative
stress.
4. Chen et al 2021 shows that Diallyl trisulfide docked to Bacterial membrane
proteins, Viral gp41 and Human GST. DATS targets membrane protein such as
NorA, OmpF, ABC transporter interact with Cysteine residue which disrupt
membrane integrity and antibiotic sensitivity. DATS bind to hydrophobic pocket of
GP 41 leads to inhibiting fusion inhibiting replication. DATS bind to active site of
GST enhances detoxification protect against oxidative stress.
5. Wang et al 2022 shows that SAMC bounds to Thioredoxin reductase,HSV1 TK,
GST. SAMC’s sulfhydryl group binds to active site of Thioredoxin reductase’s
Cysteine residue leads to inhibiting activity. SAMC’s Sulfhydril group interact with
HSV1 TK Cysteine residue leads to block vireal DNA synthesis. SAMC binds to
GSTP1 enzyme to enhance activity.
6. Li et al 2022, Kim et al 2021, Lee et al 2020 shows that Allicin, Diallyl sulfide and
Sulforaphane exhibited activity against MRSA, E coli, P aeruginosa. Allicin disrupt
MARSA, E coli and P aeruginosa. biofilm formation which enhances Oxacillin
susceptibility. Allicin target to inhibit DNA synthesis and virulence factor and cell
membrane. Diallyl sulfide inhibit MRSA, E coli and P aeruginosis growth by
reducing biofilm formation exhibiting synergic effect with vancomycin it targets to
inhibit quorum sensing and virulence factors. Sulforaphane induce MRSA growth
and induce cell death, also enhance antibiotic susceptibility with methicillin. It
target to inhibit DNA synthesis and stress response pathways and disrupt cell
membrane.
7. Choi et al 2022 and Wang et al 2021 shows that Diallylsulfide and Sulforaphane
shows activity against SARS coV 2 and HPV. Sulforaphane inhibit s SARS COV 2
replication and block viral entry and load in cell by targeting Viral protein,DNA
dependent RNA polymerase and Spike protein. In case of HPV inducing apoptosis
of HPV positive cell targeting HPV E6/E7 p53 and pRb. Diallylsulfide inhibit
SURS COV 2 replication reduces viral induce cytokinin production enhances
antiviral activity of remdesivir by inhibiting viral helicase, viral protease and host
cell protease. Diallyl sulfide inhibit DNA replication of HPV and reduce HPV
induced cell proliferation and enhance synergically antiviral activity of
podophyllotoxin. It inhibits Viral helicase, Host cell kinase and HPV E1 and E2.