Synthesis, Spectral Analysis, Molecular Docking and Biological Evaluation of Cyclohepta[b]indole Derivatives

Abstract

A new series of specifically substituted cyclohepta[b]indole derivatives from the precursor thiophen-2-ylmethylene has been synthesized. The structures of synthesized derivatives were established by spectral and elemental analyses. The docking studies with protein kinase CK2 was performed, derivative 6c exhibited the most excellent glide and E model score of –7.61 and –58.27, respectively. In-vitro anticancer activity against cervical cancer cell line (HeLa) was studied. The IC50 values were compared with the standard drug Ellipticine. Compounds 5c, 6c and 6d showed better IC50 value when compared to the other molecules. The derivatives were evaluated for their antibacterial activity against the reference drugs Sparfloxacin and Norfloxacin using agar dilution method. The derivatives 4a–d exhibited better MIC values against Gram-positive bacteria and Gram-negative bacteria when compared with remaining derivatives. Structure activity relationship (SAR) analyses established that the derivatives are potential lead compounds for future drug development studies.

Indole/isatin‐containing hybrids as potential antibacterial agents

“…Four series of indole–thiophene hybrids 52–55 (MIC: 39.5–1,957.1 μg/ml) were active against the majority of the tested B. subtilis , S. aureus , E. coli , P. vulgaris , S. typhi , P. aureus , and K. pneumoniae , and most of them (MIC: 89.5–799.7 μg/ml) were not inferior to norfloxacin (MIC: 392.3–743.4 μg/ml) against E. coli , P. vulgaris , S. typhi , and K. pneumoniae . [ 122 ] The SAR demonstrated that the introduction of pyrazole, isoxazole, and pyrimidine moieties between indole and thiophene moieties had little impact on the activity, whereas incorporation of the electron‐withdrawing group at the C‐5 position of indole moiety could boost up the activity to some extent.…”

Construction of a Pentacyclic Framework Enabled by Nickel Catalysis

“…Benzofused heterocycles, such as indole and benzofuran, have gained privileged recognition in drug discovery as important skeletal backbones of biologically active molecules, including naturally occurring alkaloids . In recent years, cyclohepta­[ b ]­indole and cyclohepta­[ b ]­benzofuran motifs have formed the basic skeletons for several naturally occurring alkaloids with a broad spectrum of therapeutic applications, drawing on antitumor, antibiotic, and anti-inflammatory properties (Scheme a) . The generation of a new functional framework is highly desired in next-generation drug discovery, yet it is always challenging.…”