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The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.

ABSTRACT: Recently, the emergence and spread of pathogenic bacterial resistance to many antibiotics (multidrug-resistant strains) have been increasing throughout the world. This phenomenon is of great concern and there is a need to find alternative chemotherapeutic agents to combat these antibiotic-resistant microorganisms. Higher plants may serve as a resource for new antimicrobials to replace or augment current therapeutic options. In this work, we have carried out a molecular docking study of a total of 561 antibacterial phytochemicals listed in the Dictionary of Natural Products, including 77 alkaloids (17 indole alkaloids, 27 isoquinoline alkaloids, 4 steroidal alkaloids, and 28 miscellaneous alkaloids), 99 terpenoids (5 monoterpenoids, 31 sesquiterpenoids, 52 diterpenoids, and 11 triterpenoids), 309 polyphenolics (87 flavonoids, 25 chalcones, 41 isoflavonoids, 5 neoflavonoids, 12 pterocarpans, 10 chromones, 7 condensed tannins, 11 coumarins, 30 stilbenoids, 2 lignans, 5 phenylpropanoids, 13 xanthones, 5 hydrolyzable tannins, and 56 miscellaneous phenolics), 30 quinones, and 46 miscellaneous phytochemicals, with six bacterial protein targets (peptide deformylase, DNA gyrase/topoisomerase IV, UDP-galactose mutase, protein tyrosine phosphatase, cytochrome P450 CYP121, and NAD?-dependent DNA ligase). In addition, 35 known inhibitors were docked with their respective targets for comparison purposes. Prenylated polyphenolics showed the best docking profiles, while terpenoids had the poorest. The most susceptible protein targets were peptide deformylases and NAD?-dependent DNA ligases.

SUBMITTER: Snow Setzer M

PROVIDER: S-EPMC5039526 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.

Snow Setzer Mary M Sharifi-Rad Javad J Setzer William N WN

Antibiotics (Basel, Switzerland) 20160912 3

Recently, the emergence and spread of pathogenic bacterial resistance to many antibiotics (multidrug-resistant strains) have been increasing throughout the world. This phenomenon is of great concern and there is a need to find alternative chemotherapeutic agents to combat these antibiotic-resistant microorganisms. Higher plants may serve as a resource for new antimicrobials to replace or augment current therapeutic options. In this work, we have carried out a molecular docking study of a total o ...[more]

PMID: 27626453

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Project description:BACKGROUND: Human African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment. METHODS: A molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14?-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4' epimerase (TbUDPGE), and ornithine decarboxylase (TbODC). RESULTS: This study revealed that triterpenoid and steroid ligands were largely selective for sterol 14?-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4' epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins. CONCLUSIONS: This in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations.

Project description:BackgroundThe first emergence of the Nipah virus (NiV) in 1998 from Malaysia became a major concern when it came to light and resurfaced on different occasions thereafter. NiV is a bat-borne zoonotic and pleomorphic virus that causes severe infection in human and animal hosts. Studies revealed fruit bats are the major reservoirs as natural hosts and pigs as intermediate hosts for the spread of this infection. This became a major concern as the disease was characterized by high pathogenicity varying from 40% to 80% depending on its acuteness. Moreover, the solemnity lies in the fact that the infection transcends from being a mere mild illness to an acute respiratory infection leading to fatal encephalitis with a reportedly high mortality rate. Currently, there is no treatment or vaccine available against the NiV. Many antiviral drugs have been explored and developed but with limited efficacy.MethodologyIn search of high-affinity ayurvedic alternatives, we conducted a pan-proteome in silico exploration of the NiV proteins for their interaction with the best-suited phytoconstituents. The toxicity prediction of thirty phytochemicals based on their LD50 value identified thirteen potential candidates. Molecular docking studies of those thirteen phytochemicals with five important NiV proteins identified Tanshinone I as the potential compound with a high binding affinity.ResultsThe pharmacokinetics and pharmacodynamics studies also aided in determining the absorption, distribution, metabolism, excretion, and toxicity of the selected phytoconstituent. Interestingly, docking studies also revealed Rosmariquinone as a potent alternative to the antiviral drug Remdesivir binding the same pocket of RNA-dependent RNA polymerase of the NiV. A molecular dynamics simulation study of the surface glycoprotein of NiV against Tanshinone I showed a stable complex formation and significant allosteric changes in the protein structure, implying that these phytochemicals could be a natural alternative to synthetic drugs against NiV.ConclusionThis study provides preliminary evidence based on in silico analysis that the herbal molecules showed an effect against NiV. However, it is essential to further evaluate the efficacy of this approach through cell-based experiments, organoid models, and eventually clinical trials.

Project description:BackgroundThe prolonged use of antibiotic viz., tetracycline, quinolones, ampicillin, etc., to reduce the infection of cholera, may failed due to the emergence of new Vibrio cholerae antibiotics resistant strains. Moreover, these antibiotics even restricted for patient suffering from severe dehydration. Hence, there is a call to find an alternative therapeutics against V. cholerae. The natures serve different herbs in its lap which might contain several natural therapeutic compounds almost all diseases. Computer-aided designing is the initial steps for screening the novel inhibitors.ObjectiveTo identify and evaluate natural compounds with low side effects with high efficacy against V. cholerae has been done.Materials and methodsIn silico screening, absorption, digestion, metabolism, and excretion (ADME), and docking of herbal compounds have been performed on to the target ToxT (transcriptional activator of V. cholerae). The compound with good ADME properties and drug-likeness property were subjected to docking.ResultsFrom 70 herbal compounds, some compounds such as aloin, campesterol, lupeol, and ursolic acid showed a violation of the rule of five and compounds such as lupeol and beta carotene showed negative binding energy. Luteolin, catechin, brevifolin, etc., compounds were selected based on ADME, drug-likeness property, and docking studies.ConclusionTwo compounds named catechin and luteolin showed better inhibition properties against ToxT and good ADME and drug-likeness property were selected as a better lead molecule for drug development in future. The Genetic Optimization for Ligand Docking fitness score for catechin is 48.74 kcal/mol and luteolin 38.12 kcal/mol.SummaryVibrio cholerae became antibiotic resistance and associated with several cholera epidemic and pandemic. Hence, there is a need to find an alternative therapeutics against V. cholerae. Many herbal compounds present in nature having high medicinal value. From in-silico study, found two compound Luteolin from Tulsi and Catechin from Green Tea which showed good binding energy and druggish property. Abbreviations used: V. cholerae: Vibrio cholera, ADME: Absorption, digestion, metabolism and excretion, CT: Cholera toxin, TCP: Toxin co-regulated Pilus, GOLD: Genetic Optimization for Ligand Docking, Asp: Aspartic acid, Arg: Arginine, Lys: Lysine, Thr: Threonine, Tyr: Tyrosine, KEGG: Kyoto encyclopedia of Genes and Genomes.

Dataset Information

The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.

Publications

The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.

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