Synthesis of novel psoralen analogues and their in vitro antitumor activity

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 17; pp. 5047 - 5053
• Main Authors: Francisco, Carla S., Rodrigues, Lígia R., Cerqueira, Nuno M.F.S.A., Oliveira-Campos, Ana M.F., Rodrigues, Lígia M., Esteves, Ana P.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2013; Elsevier
• Subjects: active sites; Adenocarcinoma; anticarcinogenic activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Antitumor activity; Aryl Hydrocarbon Hydroxylases - chemistry; Aryl Hydrocarbon Hydroxylases - metabolism; Benzofurocoumarins; Benzopsoralen analogues; Binding Sites; Biochemistry & Molecular Biology; bladder; Catalytic Domain; Cell Line, Tumor; Cell Proliferation - drug effects; cervix; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Computational studies; Cytochrome P-450 CYP2A6; Docking; Drug Screening Assays, Antitumor; enzymes; Ficusin - chemical synthesis; Ficusin - chemistry; Ficusin - toxicity; HeLa Cells; heme; Humans; Life Sciences & Biomedicine; Molecular Docking Simulation; Pharmacology & Pharmacy; Physical Sciences; psoralen; Science & Technology; Structure-Activity Relationship; structure-activity relationships; Benzofurocoumarins; Antitumor activity; Docking; Computational studies; Benzopsoralen analogues; CANCER-CELLS; CYTOCHROME-P450 2A6; ANTIPROLIFERATIVE CONSTITUENTS; FOLLOW-UP; T-CELL LYMPHOMA; COUMARINS; MECHANISM-BASED INACTIVATION; BIOLOGICAL-ACTIVITY; PLANTS; P450
• ISSN: 0968-0896; 1464-3391; 0968-0896
• DOI: 10.1016/j.bmc.2013.06.049

New tetracyclic benzofurocoumarin (benzopsoralen) analogues were synthesized and their inhibitory effect on the growth of tumor cell lines was evaluated. The human tumor cell lines used were MDA MB231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma). The in vitro antitumor activity of the new benzopsoralens was discussed in terms of structure–activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds in order to evaluate the potential of these compounds to interact with the heme group of the enzymes. The results have demonstrated that the linear compounds have the most pronounced activity against tumor cell lines and this might be related to the better accessibility that these compounds have to the active site in relation to the angular ones that have shown in the majority of the cases multiple binding poses in the active site of CYP2A6.