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- Title
Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents.
- Authors
Acuña, Julio; Piermattey, Jhoan; Caro, Daneiva; Bannwitz, Sven; Barrios, Luis; López, Jairo; Ocampo, Yanet; Vivas-Reyes, Ricardo; Aristizábal, Fabio; Gaitán, Ricardo; Müller, Klaus; Franco, Luis
- Abstract
Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series, with 15 compounds classified as active (1.73 < IC50 < 18.11 µM). The naphtho[2,3-b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2-ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest potency and selectivity. Our results suggest that the toxicity is improved in molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3-b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A 3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out, resulting in the generation of a reliable model (r² = 0.99 and q² = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents.
- Subjects
COLON cancer treatment; NAPHTHOQUINONE; CELL-mediated cytotoxicity; COMPARATIVE molecular field analysis; ANTINEOPLASTIC agents; THERAPEUTICS
- Publication
Molecules, 2018, Vol 23, Issue 1, p186
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23010186