Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2020 May 13

PMID 32392709

Citations 14

Authors

Katharigatta N Venugopala

Vijayakumar Uppar

Sandeep Chandrashekharappa

Hassan H Abdallah

Melendhran Pillay

Pran Kishore Deb

Mohamed A Morsy

Bandar E Aldhubiab

Mahesh Attimarad

Anroop B Nair

Nagaraja Sreeharsha

Christophe Tratrat

Abdulmuttaleb Yousef Jaber

Rashmi Venugopala

Raghu Prasad Mailavaram

Bilal A Al-Jaidi

Mahmoud Kandeel

Michelyne Haroun

Basavaraj Padmashali

Affiliations

Soon will be listed here.

Abstract

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-3-carboxylates - and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylates - have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylate emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.

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References

Veber D, Johnson S, Cheng H, Smith B, Ward K, Kopple K . Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002; 45(12):2615-23. DOI: 10.1021/jm020017n. View

Liu X, Xu Y, Li S, Wang Y, Peng J, Luo C . In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion. J Cheminform. 2014; 6:33. PMC: 4068908. DOI: 10.1186/1758-2946-6-33. View

Aggarwal A, Parai M, Shetty N, Wallis D, Woolhiser L, Hastings C . Development of a Novel Lead that Targets M. tuberculosis Polyketide Synthase 13. Cell. 2017; 170(2):249-259.e25. PMC: 5509550. DOI: 10.1016/j.cell.2017.06.025. View

Martin A, Morcillo N, Lemus D, Montoro E, da Silva Telles M, Simboli N . Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs. Int J Tuberc Lung Dis. 2005; 9(8):901-6. View

Lin J . CYP induction-mediated drug interactions: in vitro assessment and clinical implications. Pharm Res. 2006; 23(6):1089-116. DOI: 10.1007/s11095-006-0277-7. View

Venugopala K, Tratrat C, Pillay M, Mahomoodally F, Bhandary S, Chopra D . Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification. Antibiotics (Basel). 2019; 8(4). PMC: 6963442. DOI: 10.3390/antibiotics8040247. View

DILLARD R, PAVEY D, BENSLAY D . Synthesis and antiinflammatory activity of some 2,2-dimethyl-1,2-dihydroquinolines. J Med Chem. 1973; 16(3):251-3. DOI: 10.1021/jm00261a019. View

MIDDLEBROOK G, REGGIARDO Z, TIGERTT W . Automatable radiometric detection of growth of Mycobacterium tuberculosis in selective media. Am Rev Respir Dis. 1977; 115(6):1066-9. DOI: 10.1164/arrd.1977.115.6.1066. View

Cox E, Laessig K . FDA approval of bedaquiline--the benefit-risk balance for drug-resistant tuberculosis. N Engl J Med. 2014; 371(8):689-91. DOI: 10.1056/NEJMp1314385. View

10.

Shruthi T, Eswaran S, Shivarudraiah P, Narayanan S, Subramanian S . Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety. Bioorg Med Chem Lett. 2018; 29(1):97-102. DOI: 10.1016/j.bmcl.2018.11.002. View

11.

Rollinger J, Schuster D, Danzl B, Schwaiger S, Markt P, Schmidtke M . In silico target fishing for rationalized ligand discovery exemplified on constituents of Ruta graveolens. Planta Med. 2008; 75(3):195-204. PMC: 3525952. DOI: 10.1055/s-0028-1088397. View

12.

Pollastri M . Overview on the Rule of Five. Curr Protoc Pharmacol. 2012; Chapter 9:Unit 9.12. DOI: 10.1002/0471141755.ph0912s49. View

13.

Martins C, Carreiras M, Leon R, de Los Rios C, Bartolini M, Andrisano V . Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives, as novel tacrine analogues. Eur J Med Chem. 2011; 46(12):6119-30. DOI: 10.1016/j.ejmech.2011.09.038. View

14.

Narayanaswamy V, Albericio F, Coovadia Y, Kruger H, Maguire G, Pillay M . Total synthesis of a depsidomycin analogue by convergent solid-phase peptide synthesis and macrolactonization strategy for antitubercular activity. J Pept Sci. 2011; 17(10):683-9. DOI: 10.1002/psc.1389. View

15.

Khedr M, Pillay M, Chandrashekharappa S, Chopra D, Aldhubiab B, Attimarad M . Molecular modeling studies and anti-TB activity of trisubstituted indolizine analogues; molecular docking and dynamic inputs. J Biomol Struct Dyn. 2017; 36(8):2163-2178. DOI: 10.1080/07391102.2017.1345325. View

16.

Onodera Y, Tanaka M, Sato K . Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis. J Antimicrob Chemother. 2001; 47(4):447-50. DOI: 10.1093/jac/47.4.447. View

17.

Venugopala K, Chandrashekharappa S, Pillay M, Bhandary S, Kandeel M, Mahomoodally F . Synthesis and Structural Elucidation of Novel Benzothiazole Derivatives as Anti-tubercular Agents: In-silico Screening for Possible Target Identification. Med Chem. 2018; 15(3):311-326. DOI: 10.2174/1573406414666180703121815. View

18.

Yu D . The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol. 1999; 39(12):1203-11. DOI: 10.1177/00912709922012006. View

19.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

20.

Singh A, Venugopala K, Khedr M, Pillay M, Nwaeze K, Coovadia Y . Antimycobacterial, docking and molecular dynamic studies of pentacyclic triterpenes from Buddleja saligna leaves. J Biomol Struct Dyn. 2017; 35(12):2654-2664. DOI: 10.1080/07391102.2016.1227725. View