Synthesis of novel forskolin isoxazole derivatives with potent anti-cancer activity against breast cancer cell lines

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 18; pp. 4314 - 4318
• Main Authors: Burra, Srinivas, Voora, Vani, Rao, Ch. Prasad, Vijay Kumar, P., Kancha, Rama Krishna, David Krupadanam, G.L.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.09.2017; Elsevier
• Subjects: 1,3-Dipolar cycloadditions; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Colforsin - chemical synthesis; Colforsin - chemistry; Colforsin - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Forskolin; Humans; Isoxazoles; Isoxazoles - chemical synthesis; Isoxazoles - chemistry; Isoxazoles - pharmacology; Life Sciences & Biomedicine; MCF-7 Cells; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Regioselectivity; Science & Technology; Structure-Activity Relationship; Isoxazoles; Breast cancer; Regioselectivity; 1,3-Dipolar cycloadditions; Forskolin; CARCINOMA CELLS; ANALOGS; DOXORUBICIN; RESISTANT; INHIBITION; ACTIVATOR; EXEMESTANE; LETROZOLE; FORMESTANE
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.08.033

[Display omitted] Forskolin C1-isoxazole derivatives (3,5-regioisomers) (11a–e, 14, 15a–h and 15, 16a–g) were synthesized regioselectively by adopting 1,3-dipolar cycloadditions. These derivatives were tested using estrogen receptor positive breast cancer cell lines MCF-7 and BT-474. Majority of the compounds exhibited activity against the p53-positive MCF-7 breast cancer cells but not against the p53-negative BT-474 breast cancer cells. Among forskolin derivatives, compounds 11a, 11c, 14a, 14f, 14g, 14h, 15b, 16g and 17b exhibited higher anti-cancer activity against MCF-7 cell line with an IC50≤1µM. The derivative 14f exhibited highest activity in both p53-positive (MCF-7) and p53-negative (BT-474) breast cancer cell lines with an IC50 of 0.5µM.