Synthesis of novel chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives via domino aldol-type/hetero Diels–Alder reaction and their cytotoxicity evaluation

• Published in: Bioorganic & medicinal chemistry letters 2014-09, Vol.24 (18), p.4428-4434
• Main Authors: Madda, Jyothi, Venkatesham, Akkaladevi, Naveen Kumar, Bejjanki, Nagaiah, Kommu, Sujitha, Pombala, Ganesh Kumar, C., Rao, Tadikamalla Prabhakar, Jagadeesh Babu, Nanubolu
• Format: Article
• Language: English
• Subjects: A549 (lung); Aldol-type/hetero Diels–Alder reaction cytotoxicity evaluation; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Chromeno pyrano[3,4-c]benzopyran and naphtho pyrans; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HEK293 Cells; HeLa (cervical); HeLa Cells; Humans; MCF-7 (breast); MCF-7 Cells; MDA-MB-231 (breast); Models, Molecular; Molecular Structure; Naphthols - chemical synthesis; Naphthols - chemistry; Naphthols - pharmacology; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.08.005

New chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives have been synthesized by domino aldol-type reaction/hetero Diels–Alder reaction generated from o-quinone methide in situ from 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones with resorcinols/naphthols in the presence of 20mol% ethylenediamine diacetate (EDDA), triethylamine (2mL) as co-catalyst in CH3CN under reflux conditions in good yields. The structures were established based on spectroscopic data, and further confirmed by X-ray diffraction analysis. The results showed that compounds 4h and 4j exhibited very potent cytotoxicity against human cervical cancer cell line (HeLa). Compound 4h displayed good inhibitory activity against both breast cancer cell lines, MDA-MB-231 and MCF-7. Further, the compound 4i exhibited good cytotoxicity against only MDA-MB-231, and compound 4j showed promising activity against human lung cancer cell line, A549 with IC50 value of 2.53±0.07μM, which was comparable to the standard doxorubicin (IC50=1.21±0.1μM).