Synthesis, Antitumor Activity and Docking of 2,3-(Substituted)-1,4-Naphthoquinone Derivatives Containing Nitrogen, Oxygen and Sulfur

• Published in: Journal of the Brazilian Chemical Society Vol. 26; no. 9; pp. 1804 - 1816
• Main Authors: Delarmelina, Maicon, Daltoe, Renata D., Cerri, Murilo F., Madeira, Klesia P., Rangel, Leticia B. A., Lacerda Junior, Valdemar, Romao, Wanderson, Taranto, Alex G., Greco, Sandro J.
• Format: Journal Article
• Language: English; Portuguese
• Published: SAO PAULO Soc Brasileira Quimica 01.09.2015; Sociedade Brasileira de Química
• Subjects: Chemistry; CHEMISTRY, MULTIDISCIPLINARY; Physical Sciences; Science & Technology; TOPOISOMERASE-II; NAPHTHOQUINONE DERIVATIVES; POTENT ANTIFUNGAL; ANTIBACTERIAL; IN-VITRO; PI3K; antineoplastic activity; nucleophilic substitution; 1,4-NAPHTHOQUINONE DERIVATIVES; BIOLOGICAL EVALUATION; topoisomerase; CONTAINING HETERO-1,4-NAPHTHOQUINONES; OPTIMIZATION; 1,4-naphthoquinone; WATER
• ISSN: 0103-5053; 1678-4790; 1678-4790
• DOI: 10.5935/0103-5053.20150157

Eleven 2,3-(substituted)-1,4-naphthoquinone derivatives were synthesized in yields ranging from 52-89%. These derivatives were evaluated for their cytotoxic effects on human lungs (H460), triple-negative breast (MDA-MB-231) and ovarian (A2780) cancer cell lines. Compounds 5f and 8 showed IC50 values of 3.048 x 10(-5) mol L-1 and 4.24 x 10(-6) mol L-1 for H460; 5c and 8 showed IC50 values of 2.16 x 10(-5) mol L-1 and 1.60 x 10(-5) mol L-1 for MDA-MB-231, and 5g and 8 showed IC50 values of 2.68 x 10(-6) mol L-1 and 3.89 x 10(-6) mol L-1 for A2780. Additionally, we conducted a docking study with the four most active compounds and the therapeutic targets PI3K and topoisomerase II showing the pharmacophoric conformation of these compounds.