Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds

Abstract

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.