Chahal Sandhya, Rani Payal, Singh Rajvir, Joshi Gaurav, Kumar Roshan, Kumar Parvin, Wadhwa Deepak, Singh Devender, Sindhu Jayant
Department of Chemistry, COBS&H, CCS Haryana Agricultural University, Hisar, 125004, India.
Department of Pharmaceutical Science, Hemvati Nandan Bahuguna Garhwal (A Central) University, Srinagar, Dist. Garhwal, Uttarakhand, 246174, India.
Future Med Chem. 2024;16(21):2231-2245. doi: 10.1080/17568919.2024.2400968. Epub 2024 Sep 20.
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. 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 preliminary screening against A549 based lung cancer cell line at 5 μM. Compound 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 IC against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound has been selected for further studies, as it demonstrated significant cytotoxicity, while compound showed no effect on gene expression but upregulated gene expression, suggesting a role in managing diabetes. Compound exhibited the ability to decrease expression and increase expression, indicating its potential for treating both diabetes and cancer.
血液中淀粉酶水平升高，即高淀粉酶血症，已被证明与糖尿病和癌症有关。为了研究高淀粉酶血症对细胞增殖的影响，设计同时靶向α-淀粉酶活性和癌症进展的双重抑制剂至关重要。使用多组分反应合成了萘醌稠合二氮杂卓，其生态评分高达87，并通过抗氧化和α-淀粉酶抑制试验评估了其生物功效。在5μM浓度下对A549肺癌细胞系进行初步筛选，已初步建立了糖尿病与癌症之间的关联。化合物分别表现出优于丁基羟基甲苯（BHT）和阿卡波糖的抗氧化和α-淀粉酶抑制潜力，其抑制模式为非竞争性。然后研究了抑制率超过50%的化合物对A549（肺癌）、乳腺癌（MCF-7和MDA-MB-231）细胞的半数抑制浓度（IC）。其中，化合物已被选作进一步研究对象，因为它表现出显著的细胞毒性，而化合物对基因表达无影响，但上调了基因表达，表明其在控制糖尿病方面的作用。化合物表现出降低表达和增加表达的能力，表明其在治疗糖尿病和癌症方面的潜力。
