Naphthoquinone fused diazepines targeting hyperamylasemia: potential therapeutic agents for diabetes and cancer

<b>Aim:</b> Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.<b>Materials & methods:</b> Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established <i>via</i> preliminary screening against A549 based lung cancer cell line at 5 μM.<b>Results & conclusion:</b> Compound <b>4b</b> exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC₅₀ against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound <b>4p</b> has been selected for further studies, as it demonstrated significant cytotoxicity, while compound <b>4b</b> showed no effect on <i>AKT</i> gene expression but upregulated <i>IGF-1R</i> gene expression, suggesting a role in managing diabetes. Compound <b>4p</b> exhibited the ability to decrease <i>AKT</i> expression and increase <i>IGF-1R</i> expression, indicating its potential for treating both diabetes and cancer.