Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents

Autor: Yanet Ocampo, Jairo López, Sven Bannwitz, Jhoan Piermattey, Luis A. Franco, Ricardo Vivas-Reyes, Daneiva Caro, Ricardo Gaitan, Julio Acuña, Luis Barrios, Fabio Aristizábal, Klaus Müller
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Models
Molecular
Quantitative structure–activity relationship
colorectal cancer
naphthoquinone derivatives
anti-proliferative activity
3D-QSAR
Cell Survival
Molecular Conformation
Pharmaceutical Science
Quantitative Structure-Activity Relationship
Antineoplastic Agents
Chemistry Techniques
Synthetic
Pharmacology
Article
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
chemistry.chemical_compound
Inhibitory Concentration 50
0302 clinical medicine
lcsh:Organic chemistry
Cell Line
Tumor
Drug Discovery
medicine
Potency
Humans
Physical and Theoretical Chemistry
Cytotoxicity
IC50
Cell Proliferation
chemistry.chemical_classification
Molecular Structure
Organic Chemistry
Cancer
medicine.disease
Naphthoquinone
030104 developmental biology
chemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Drug Design
Toxicity
Molecular Medicine
Colorectal Neoplasms
Tricyclic
Naphthoquinones
Zdroj: Molecules, Vol 23, Iss 1, p 186 (2018)
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules; Volume 23; Issue 1; Pages: 186
ISSN: 1420-3049
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje