Synthesis, crystal structure and antimycobacterial activities of 4-indolyl-1,4-dihydropyridine derivatives possessing various ester groups

• Published in: Research on chemical intermediates Vol. 43; no. 12; pp. 7471 - 7489
• Main Authors: Baydar, Ece, Gündüz, Miyase Gözde, Krishna, Vagolu Siva, Şimşek, Rahime, Sriram, Dharmarajan, Yıldırım, Sema Öztürk, Butcher, Ray J., Şafak, Cihat
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2017; Springer Nature B.V
• Subjects: Catalysis; Chemistry; Chemistry and Materials Science; Crystal structure; Derivatives; Infrared radiation; Inorganic Chemistry; NMR; Nuclear magnetic resonance; Physical Chemistry; Synthesis; Toxicity; Tuberculosis; X ray analysis; Cytotoxicity; Docking; Hexahydroquinoline; 1,4-dihydropyridine; Antimycobacterial activity; Structural analysis
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-017-3087-0

The present study reports the synthesis of a series of alkyl 4-(5/6-bromo
-
1H-indole-3-yl)-2,6,6/2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate derivatives by a simple, rapid and convenient modified Hantzsch condensation reaction under microwave irradiation. The structure elucidation of the target compounds was carried out by different spectral techniques including IR,
1
H-NMR, COSY,
13
C-NMR, and mass analysis. Additionally, the proposed structure of compound
3
was proved by single crystal X-ray analysis. In vitro anti-tubercular activity of the compounds was evaluated against
Mycobacterium tuberculosis
H
37
Rv. The obtained results indicated that some compounds exhibited moderate antimycobacterial activity with weak cytotoxicity. Among them, compounds carrying ethyl or isopropyl groups in their ester moiety were found to be the most active compounds in this series. Molecular modeling studies were carried out to gain an idea about the mechanism of action of the active compounds. According to the results, the interactions were found quite similar with the co-crystalized ligand of
M. tuberculosis
enoyl reductase (InhA).