title: 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.
abstract: 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 20 mol% ethylenediamine diacetate (EDDA), triethylamine (2 mL) 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±0.07 μM, which was comparable to the standard doxorubicin (IC50=1.21±0.1 μM).
authors.affiliation: Division of Organic and Biomolecular Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Madda
authors.affiliation: Division of Organic and Biomolecular Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Akkaladevi
authors.initials: A
authors.lastname: Venkatesham
authors.affiliation: Division of Organic and Biomolecular Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Bejjanki
authors.initials: B
authors.lastname: Naveen Kumar
authors.affiliation: Division of Organic and Biomolecular Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: nagaiah@iict.res.in.
authors.forename: Kommu
authors.initials: K
authors.lastname: Nagaiah
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Pombala
authors.initials: P
authors.lastname: Sujitha
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: C
authors.initials: C
authors.lastname: Ganesh Kumar
authors.affiliation: Center for Nuclear Magnetic Resonance, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Tadikamalla Prabhakar
authors.initials: TP
authors.lastname: Rao
authors.affiliation: X-ray Crystallography Laboratory, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Nanubolu
authors.initials: N
authors.lastname: Jagadeesh Babu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D009284:Naphthols; D011714:Pyrans; C000596631:pyrano(3,4-c)benzopyran
keywords: A549 (lung); Aldol-type/hetero Diels–Alder reaction cytotoxicity evaluation; Chromeno pyrano[3,4-c]benzopyran and naphtho pyrans; HeLa (cervical); MCF-7 (breast); MDA-MB-231 (breast)