Design, synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

被引:14
作者
Bodige, Srinu [1 ]
Ravula, Parameshwar [2 ]
Gulipalli, Kali Charan [1 ]
Endoori, Srinivas [1 ]
Cherukumalli, Purna Koteswara Rao [1 ]
Chandra, Narendra Sharath J. N. [3 ]
Seelam, Nareshvarma [1 ]
机构
[1] Koneru Lakshmaiah Educ Fdn, Dept Chem, Vaddeswaram 522502, Guntur, India
[2] Sch Pharm, Dept Pharmaceut Chem, Gurunanak Inst Tech Campus, Hyderabad, India
[3] Guruktupa Inst Pharm, Dept Pharmaceut Chem, Majalgaon, Maharashtra, India
关键词
Antitubercular activity; 1,4-azaindoles; docking studies; synthesis; MYCOBACTERIUM-TUBERCULOSIS; DPRE1; INHIBITORS;
D O I
10.1080/00397911.2019.1618874
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, H-1 NMR, C-13 NMR, F-19 NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12 mu g/mL) in comparison with reference drug, Pyrazinamide ((3.12 mu g/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.
引用
收藏
页码:2219 / 2234
页数:16
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