Virtual screening of novel pyridine derivatives as effective inhibitors of DNA gyrase (GyrA) of salmonella typhi

Philip, J.; Uzairu, A.; Shallangwa, G.; Uba, S.

Growing Science » Current Chemistry Letters » Virtual screening of novel pyridine derivatives as effective inhibitors of DNA gyrase (GyrA) of salmonella typhi

Journals

CCL Volumes

Volume 1 (23)
- Issue 1 (7)
- Issue 2 (5)
- Issue 3 (6)
- Issue 4 (5)

Volume 2 (26)
- Issue 1 (7)
- Issue 2 (6)
- Issue 3 (6)
- Issue 4 (7)

Volume 3 (30)
- Issue 1 (7)
- Issue 2 (10)
- Issue 3 (8)
- Issue 4 (5)

Volume 4 (21)
- Issue 1 (5)
- Issue 2 (5)
- Issue 3 (6)
- Issue 4 (5)

Volume 5 (20)
- Issue 1 (5)
- Issue 2 (5)
- Issue 3 (5)
- Issue 4 (5)

Volume 6 (20)
- Issue 1 (5)
- Issue 2 (5)
- Issue 3 (5)
- Issue 4 (5)

Volume 7 (15)
- Issue 1 (4)
- Issue 2 (4)
- Issue 3 (4)
- Issue 4 (3)

Volume 8 (20)
- Issue 1 (5)
- Issue 2 (5)
- Issue 3 (5)
- Issue 4 (5)

Volume 9 (20)
- Issue 1 (5)
- Issue 2 (5)
- Issue 3 (5)
- Issue 4 (5)

Volume 10 (43)
- Issue 1 (5)
- Issue 2 (7)
- Issue 3 (17)
- Issue 4 (14)

Volume 11 (43)
- Issue 1 (14)
- Issue 2 (11)
- Issue 3 (10)
- Issue 4 (8)

Volume 12 (78)
- Issue 1 (21)
- Issue 2 (22)
- Issue 3 (20)
- Issue 4 (15)

Volume 13 (68)
- Issue 1 (23)
- Issue 2 (17)
- Issue 3 (16)
- Issue 4 (12)

Countries

Current Chemistry Letters

ISSN 1927-730x (Online) - ISSN 1927-7296 (Print) Quarterly Publication Volume 12 Issue 1 pp. 1-16 , 2023

Virtual screening of novel pyridine derivatives as effective inhibitors of DNA gyrase (GyrA) of salmonella typhi Pages 1-16 Download PDF

Authors: John Ameji Philip, Adamu Uzairu, Gideon Adamu Shallangwa, Sani Uba

DOI: 10.5267/j.ccl.2022.10.002

Keywords: Pyridine, DNA gyrase, Salmonella typhi, Pharmacokinetics, Drug-likeness

Abstract: In a bid to discovering novel antibiotics to combat growing trend of multi-drug resistance strains of Salmonella typhi, 48 new pyridine derivatives with significant inhibitory activities against the aforementioned bacterium were subjected to molecular docking against DNA gyrase protease of the bacterium, drug likeness evaluation and pharmacokinetics profiling. All the 48 leads displayed better binding affinity values when compared with Amoxicillin, Ciprofloxacin, Ceftriaxone, Ampicillin, and chloramphenicol, the standard antibiotics used herein for quality assurance. Furthermore, the majority of the compounds were, however, screened out due to their poor pharmacokinetics profiles and drug-likeness. Only five compounds emerged as the most promising leads and they include C4 with binding affinity of -8.0 kcal/mol, C8 (-8.6 kcal/mol), C9 (-8.1 kcal/mol), C26 (-8.3 kcal/mol), and C27 (-8.0 kcal/mol). These compounds not only displayed better binding affinity when compared with the reference antibiotics but also exhibit different modes of interactions with the target protease of the bacterium making them more potent and drug like. Toxicity evaluation of the leads also revealed that the compounds are neither tumorigenic nor mutagenic. In view of the excellent binding affinity, high pharmacokinetics profile and positive drug-likeness of the novel ligands, we recommend these promising compounds for in vitro and in vivo studies in order to discover novel antibiotics that could curb the dangerous trend of multiple drug resistance by Salmonella typhi.

How to cite this paper

 Philip, J., Uzairu, A., Shallangwa, G & Uba, S. (2023). Virtual screening of novel pyridine derivatives as effective inhibitors of DNA gyrase (GyrA) of salmonella typhi.Current Chemistry Letters, 12(1), 1-16.

Refrences

1. Fauci A.S., Kasper D.L., Longo D.L., Braunwald E., Hauser S.L., Jameson J.L., Loscalzo J. (2008) Harrison´s Principles of Internal Medicine, 17th edition. Internal Medicine Journal, 38 (12) 932-932, https://doi.org/10.1111/j.1445-5994.2008.01837.x
2. World Health Organization (2018) Typhoid. Retrieved from http://www.who.int/news-room/fact-sheets/detail/typhoid on September 5, 2022
3. Gasem M.H., Dolmans W.M., Keuter M.M., Djokomo eljanto R.R. (2001) Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia. Trop Med Int Health, 6(6) 484-490, https://doi: 10.1046/j.1365-3156.2001.00734. x.
4. Dewan A.M., Corner R., Hashizume M., Ongee E.T. (2013) Typhoid Fever and its association with environmental factors in the Dhaka Metropolitan Area of Bangladesh: a spatial and time-series approach. PLOS Neglected Tropical Disease. 7(1): p.e1998. https://doi: 10.1371/journal.pntd.0001998 PMID: 23359825
5. Khan M.I., Ochiai R.L., Soofi L.V., Khan M.J., Sahito S.M., Habib M.A., Puri J.K., You Y.A. (2012) Risk factors associated with typhoid fever in children aged 2–16 years in Karachi, Pakistan. Epidemiol Infect., 140(4) 665–72. doi: 10.1017/S0950268811000938 PMID: 21676350
6. Klemm E.J., Shakoor S., Page A.J., Qamar F.N., Judge K., Saeed D.K., Wong V.K., Dallman T.J., Nair S., Baker S., Shaheen G., Qureshi S., Yousafzai M.T., Saleem M.K., Hasan Z., Dougan G., Hasan R. (2018) Emergence of an extensively drugresistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio 9:e00105-18. https://doi.org/10.1128/mBio .00105-18.
7. Peirano G., Van der B.I.J., Freeman K.A., Poirel L.J., Nordmann L., Costello P., et al. (2014) Characteristics of Escherichia coli sequence type 131 isolates that produce extended-spectrum _-lactamases: Global distribution of the H 30-Rx sublineage. Antimicrob. Agents Chemother, 58 3762–3767.
8. Smith S.M., Palumbo P.E., Edelson P.J. (1984) Salmonella strains resistant to multiple antibiotics: Therapeutic implications. Pediatric Infect. Dis., 3 455–460.
9. Chen S., Cui S., McDermott P.F., Zhao S., White D.G., Paulsen I., Meng J. (2007) Contribution of target gene mutations and efflux to decreased susceptibility of Salmonella enterica serovar Typhimurium to fluoroquinolones and other antimicrobials. Antimicrob. Agents Chemother, 51 535–542.
10. Gaind R., Paglietti B., Murgia M., Dawar R., Uzzau S., Cappuccinelli P., Deb M., Aggarwal P., Rubino S. (2006) Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India. J. Antimicrob. Chemother, 58 1139–1144.
11. Hirose K., Hashimoto A., Tamura K., Kawamura Y., Ezaki T., Sagara H., Watanabe H. (2002) DNA sequence analysis of DNA gyrase and DNA topoisomerase IV quinolone resistance-determining regions of Salmonella enterica serovar Typhi and serovar Paratyphi A. Antimicrob. Agents Chemother, 46 3249–3252.
12. Menezes G.A., Harish B.N., Khan M.A., Goessens W., Hays J. (2016) Antimicrobial resistance trends in blood culture positive Salmonella Paratyphi A isolates from Pondicherry, India. Indian J. Med. Microbiol, 34 222–227.
13. Anebi E.I., Shallangwa M.T., Isyaku G.A., Abdulsalam S.S., Danmallam A.M. (2020) Molecular docking study, drug-likeness and pharmacokinetic properties (ADMET) prediction of some novel thiophene derivatives as salmonella typhi inhibitors, Bayero Journal of Pure and Applied Sciences, 14 (2). doi: 10.4314/bajopas.v14i2.29
14. Abhishek K.V., Aminu I.D., Avinash K., Binta S.S., Umar A.H., Najib L.Y., Usman R.B., Zaharaddeen U.N., Abubakar D.D. (2020) Virtual Screening, Molecular Docking, and ADME/T Analysis of Natural Product Library against Cell Invasion Protein SipB from Salmonella enterica serotype typhi: In Silico Analysis”. Acta Scientific Pharmaceutical Sciences 4 (8) 20-30. DOI:10.31080/ASPS.2020.04.0563
15. Arunkumar M., Murugan M., Vairamuthu A., Manikka K.A., Sathaiah G., Verma M., Balasubramaniem A., Perumal V. (2022) Evaluation of seaweed sulfated polysaccharides as natural antagonists targeting Salmonella typhi OmpF: molecular docking and pharmacokinetic profiling. Beni-Suef Univ J Basic Appl Sci, 11(8)
16. Mamaghani M., Tabatabaeian K., Bayat M., Nia R.H., Rassa M. (2013) Regioselective Synthesis and Antibacterial Evaluation of a New Class of Substituted Pyrazolo[3,4-b] Pyridines. J. Chem. Res., 37 494–498.
17. Anderson D.R., Hegde S., Reinhard E., Gomez L., Vernier W.F., Lee L., Liu S., Sambandam A., Snider P.A., Masih L. (2005) Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorganic Med. Chem. Lett., 15 1587–1590.
18. Zhang X., Qiu Y., Li X., Bhattacharjee S., Woods M., Kraft P., Lundeen S.G., Sui Z. (2009) Discovery and structure–activity relationships of a novel series of benzopyran-based KATP openers for urge urinary incontinence. Bioorganic Med. Chem., 17, 855–866.
19. Samadi A., Marco-Contelles J., Soriano E., Álvarez-Pérez M., Chioua M., Romero A., González-Lafuente L., et al., (2010) Multipotent drugs with cholinergic and neuroprotective properties for the treatment of Alzheimer and neuronal vascular diseases. I. Synthesis, biological assessment, and molecular modeling of simple and readily available 2-aminopyridine-, and 2-chloropyridine-3,5-dicarbonitriles. Bioorganic Med. Chem., 18, 5861–5872
20. Hamada Y (2018). Role of Pyridines in Medicinal Chemistry and Design of BACE1 Inhibitors Possessing a Pyridine Scaffold. In Pyridine, Pandey, P.P., Ed.; IntechOpen: London, UK, 10–29
21. Ling Y., Hao Z.Y., Liang D., Zhang C.L., Liu Y.F., Wang Y. (2021) The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design. Drug Des. Devel., 15 4289–4338.
22. Altaf A.A., Shahza A., Gul Z., Rasool N., Badshah A., Lal B., Khan E. (2015) A Review on the Medicinal Importance of Pyridine Derivatives. J. Drug Des. Med. Chem., 1; 1–11.
23. Zalaru C., Dumitrascu F., Draghici C., Tarcomnicu I., Tatia R., Moldovan L., Chifiriuc M.C., Lazar V., Marinescu M., Nitulescu M.G., et al. (2018) Synthesis, spectroscopic characterization, DFT study and antimicrobial activity of novel alkylaminopyrazole derivatives. J. Mol. Struct., 1156 12–21.
24. Marinescu M., Cinteza L.O., Marton G.I., Chifiriuc M.C., Popa M., Stanculescu I., Zalaru C.M., Stavarache C.E. (2020) Synthesis,density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases. BMC Chem., 14, 45.
25. Marinescu M. (2021) Synthesis of Antimicrobial Benzimidazole–Pyrazole Compounds and Their Biological Activities. Antibiotics, 10 1002.
26. Lad B.H., Giri R.R., Chovatiya L.Y., Brahmbhatt I.D. (2015) Synthesis of modified pyridine and bipyridine substituted coumarins as potent antimicrobial agents. J. Serb. Chem. Soc, 80 (6) 739–747, https://doi: 10.2298/JSC140804004L
27. Mungra C.D., Patel P.M., Patel G.R. (2009) An efficient one-pot synthesis and in vitro antimicrobial activity of new pyridine derivatives bearing the tetrazoloquinoline nucleus. ARKIVOC, 14 64-74.
28. Daina A., Michielin O., Zoete V. (2017) SwissADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. SCientifiC REpOrtS, 7 42717 DOI: 10.1038/srep42717
29. Konig J., Muller F., (2013) Transporters and drug-drug interractions: Important determinants of drug disposition and effects. Phamacol Rev, 65 944-966