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Albany 2019: 20th Conversation - Abstracts

Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Carboline derivative compounds targeting DNA: Synthesis, binding and in vitro cytotoxicty on human cancer cell lines

Three sets of carboline derived compounds were prepared by Pictet-Spengler cyclization. These tetrahydro beta- and gamma-carbolines have CF3 group with an additional amino alkyl chains (α- or δ-position) and guanidine alkyl chains (α-position), of varying length. Structure–activity relationship of these molecules with calf thymus DNA was emphasized by fluorescence, ITC, FTIR and viscosity. Binding with DNA resulted in dramatic enhancement and quenching in the fluorescence emission. Gamma-carboline analogs showed maximum DNA binding followed by beta-carboline compounds with amino alkyl chain and least with guanidine alkyl chain compounds. It decreased with increasing chain length. The bindings were entropically driven being more with guanidine alkyl chain analogs. Site preference and mode of binding with partial intercalation and external binding was supported by FTIR and viscosity. Cytotoxic potencies of the compounds were tested on seven different cancer cell lines. The smallest alkyl chain analog attached to gamma position, Comp3, showed maximum cytotoxicity with GI50 6.2 µM, against HCT-116 causing apoptosis, followed by the guanidine alkyl chain compounds, but amino alkyl chain compounds to beta position showed poor cytotoxicity.

These results may be of prospective use in a framework to design novel carboline derivatives as antitumor drugs for improved therapeutic applications in future.

I would like to acknowledge Prof. Valentine Nenajdenko and team from Moscow State University, Moscow, for the synthesis of the compounds and also grateful to DST-RFBR 2017-19 for funding of the research.

Kakali Bhadra, Ph.D.

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Dr. Kakali Bhadra is an Assistant Professor at Univ. of Kalyani, India and will provide a short oral from the platform.

University of Kalyani
Assistant Professor
Department of Zoology
Kalyani, 74123 India

e-mail: kakali_bhadra2004@yahoo.com