Synthesis and Human Anticancer Cell Line Studies on Coumarin-β-carboline Hybrids as Possible Antimitotic Agents
Graphical Abstract
New molecular entities were synthesized by the combination of naturally occurring coumarins and β-carbolines. The formation of novel C4-C1 bridged coumarin tetrahydro-β-carboline was achieved in excellent yields via Pictet-Spengler cyclisation. Comparative cell line inhibition study of coumarin tetrahydro-β-carbolines, coumarin dihydro-β-carbolines and coumarin-β-carbolines were studied. Among these, ring C aromatized coumarin-β-carboline was found to be more active against human cancer cell lines and the unique ability to interact with both tubulin and KSP proteins was supported by in-silico studies.
Abstract
A series of coumarin tetrahydro-β-carboline hybrids 3 have been synthesized by the Pictet-Spengler reaction. Stoichiometrically controlled DDQ oxidation has led to dihydro 4 and β-carboline 5. In vitro anticancer activity against 60 cell lines has revealed the potency of 3 f, 4 a and 5 c. In silico studies indicate the binding properties of 5 c with Kinesin spindle protein (KSP) and tubulin protein. Gel electrophoresis studies revealed that compound 3 f partially cleaved the CT-DNA, whereas the ring C aromatized compound 5 c completely cleaved the CT-DNA. Structures of the newly synthesized compounds are confirmed by spectroscopic and X-ray studies.
