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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

S16020 Pyridocarbazole Derivatives Display High Activity to Lung Cancer Cells

Author(s): Gabriela Chabowska, Helena Moreira*, Beata Tylińska and Ewa Barg*

Volume 22, Issue 13, 2022

Published on: 06 April, 2022

Page: [2419 - 2428] Pages: 10

DOI: 10.2174/1871520621666211214104926

Price: $65

Abstract

Background: Despite the dynamic development of medicine, globally cancer diseases remain the second leading cause of death. Therefore, there is a strong necessity to improve chemotherapy regimens and search for new anticancer agents. Pyridocarbazoles are compounds with confirmed antitumor properties based on multimodal mechanisms, i.e. DNA intercalation and topoisomerase II-DNA complex inhibition. One of them, S16020, displayed a wide spectrum of activity.

Objective: The aim of the study was to investigate the antitumor potency of six S16020 derivatives, synthesized according to the SAR (structure-activity relationship) method.

Methods: The biological evaluation included influence on cancer cell viability, proliferation, and migration, as well as P-glycoprotein activity. NHDF, A549, MCF-7, LoVo, and LoVo/DX cell lines were used in the study.

Results: All derivatives displayed low toxicity to normal (NHDF) cells at 1 and 2 μM (≤ 20% of cell growth inhibition). The highest reduction in cell viability was noted in A549 cells, which was accompanied by significant disruption of cells proliferation and motility. Compound 1 exhibited the strongest cytotoxic, antiproliferative, and antimigratory effects, higher than the reference olivacine. A significant reduction in P-glycoprotein activity was found for derivatives 6 and 1.

Conclusion: S16020 derivatives could be considered as potential candidates for new anticancer drugs.

Keywords: Pyridocarbazole, S16020, olivacine, SAR, anticancer drugs, p-glycoprotein inhibitor, cancer cells migration.

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