Synthesis, molecular docking and in vitro antiproliferative activity of novel pyrano[3,2-c]carbazole derivatives†
Abstract
A new series of polycyclic pyrano[3,2-c]carbazole derivatives have been synthesized by domino Knoevenagel–hetero-Diels–Alder reactions. The key strategy involves ethylenediamine diacetate (EDDA) catalyzed cyclization of the O-prenyl derivative of N-Boc-carbazole-3-carboxaldehyde with cyclic 1,3-diketones or pyrazol-5-ones to afford cis-fused N-Boc-pyrano[3,2-c]carbazole derivatives. The reactions were clean and highly diastereoselective, affording the desired products in good yields. The deprotection of the Boc group under acidic conditions led to pyrano[3,2-c]carbazole derivatives. The antiproliferative activity of all the synthesized compounds on three cancer cell lines such as PANC 1 (pancreatic), HeLa (cervical) and MDA-MB-231 (breast cancer) was investigated. The results clearly demonstrated that compounds 12d, 12f and 12g displayed pronounced antiproliferative activity. In addition, the antimicrobial activity of these compounds was also assayed against three representative Gram-positive organisms and Gram-negative organisms. Specifically, compound 12d exhibited significant antimicrobial activity. Molecular docking studies revealed that the lead compounds selectively occupy the colchicine binding site of tubulin.
![Graphical abstract: Synthesis, molecular docking and in vitro antiproliferative activity of novel pyrano[3,2-c]carbazole derivatives](/en/Image/Get?imageInfo.ImageType=GA&imageInfo.ImageIdentifier.ManuscriptID=C6NJ01580H&imageInfo.ImageIdentifier.Year=2016)
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