Indole-Fused Benzooxazepines: a New Structural Class of Anticancer Agents

Abstract

Aim:A new series of compounds (1a–16a) bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.Materials & methods:In this study, all the synthesized compounds were screened via in vitro anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.Results:Some of the synthesized compounds effectively controlled the growth of cancerous cells.Conclusion:The most active compounds – 6a, 10a, 13a, 14a and 15a – exemplify notable anticancer profile with GI50 <10 μg/ml. Preliminary structure–activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π–π stacking interactions, with good ADMET profiling and molecular dynamic simulation.

Chalcone derived benzoheterodiazepines for medicinal applications: A Two‐pot and one‐pot synthetic approach

“…Chalcone is a natural product [1] and bio-active [2,3] molecule that frequently used in the synthesis of heterocyclic compounds that is, pyrazole [4], imidazole [5,6], epoxide [7], benzodiazepine [8], pyrimidine [9], indole [10], flavone [11], isoflavone [12], and pyrazoline [13][14][15]. Chalcone-derived heterocyclic compounds consist of heteroatomic atoms (i.e., oxygen, sulfur, and nitrogen), which remarkable in the medicinal field for excellent activities in drug design [16][17][18]. Benzoheterodiazepine is a seven-membered heterocyclic ring [19] with two heteroatoms [20], nonplanar [21], and pharmacophoric [22,23] properties.…”

Determination of 5h-Benzo[2,3][1,4]oxazepino[5,6-B]indoles in Rat Plasma by Reversed-Phase High-Performance Liquid Chromatographic-Ultraviolet Method: Application to Pharmacokinetic Studies

“…In view of the aforementioned facts, recently [15], we designed and synthesized a new structural class indole-fused benzooxazepines (IFBO), particularly 5H-benzo [2,3] [1,4]oxazepino [5,6-b]indoles derivatives, on the basis of molecular modeling on various related targets and evaluated them for in vitro antitumor potency against hepatocellular carcinoma (HCC)-specific Hep-G2 cell lines. Three compounds such as 6a, 10a, and 15a ( Fig.…”

“…All the compounds 6a, 10a, and 15a were synthesized previously in our laboratory using the chemicals provided by Sigma-Aldrich and Himedia [15]. All other reagents used were of analytical grade.…”