Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Andhra Pradesh 515134, India.
Bioengineering and Drug Design Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology, Madras, Tamil Nadu 600036, India.
Bioorg Med Chem Lett. 2020 Jun 15;30(12):127199. doi: 10.1016/j.bmcl.2020.127199. Epub 2020 Apr 18.
Spirobibenzopyrans are an unexplored class of therapeutics. We report the anticancer activity of novel spirobibenzopyrans, synthesized by a one-pot reaction and extensively characterized. Structure of one of the spirobibenzopyran has been determined by the single crystal XRD technique. The in vitro anticancer activity of these derivatives across the NCI 60-cell line panel was evaluated and for the first time their mechanism of action against HeLa cells was probed via cell morphology analysis and cell cycle analysis. They were determined to be apoptosis inducers with cell cycle arrest in G/G and S phase suggesting CDK-4 protein inhibition and the inhibition of DNA replication. The DNA inhibition was studied and confirmed using the alkaline comet assay for the compound CHX-4MO-SAL showing S phase inhibition. Further, conformity with the in silico Lipinski's score signify the potential of spirobibenzopyrans as anticancer leads.
螺环苯并吡喃是一类尚未开发的治疗药物。我们报告了新型螺环苯并吡喃的抗癌活性，这些化合物是通过一锅反应合成的，并进行了广泛的表征。其中一个螺环苯并吡喃的结构通过单晶 X 射线衍射技术确定。评估了这些衍生物在 NCI 60 细胞系面板上的体外抗癌活性，并首次通过细胞形态分析和细胞周期分析研究了它们针对 HeLa 细胞的作用机制。它们被确定为凋亡诱导剂，细胞周期停滞在 G/G 和 S 期，表明 CDK-4 蛋白抑制和 DNA 复制抑制。使用碱性彗星试验研究并证实了化合物 CHX-4MO-SAL 的 DNA 抑制作用，表明其具有 S 期抑制作用。此外，与基于计算机的利宾斯基评分相符，表明螺环苯并吡喃具有作为抗癌先导的潜力。
