title: Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents.
abstract: In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a-p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI50<0.1 and 4μM respectively) as good as adriamycin (GI50<0.1μM). The compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells. The effect of extended conjugation on activity authenticated by comparing activity profile of compound 5a, 5i and 5m with their simple analogues. Among the synthesized compounds, 5i and 5l were found to be active anti-inflammatory agents in addition to having noteworthy antioxidant potential. These results suggest the possible use of these compounds for the design and development of novel anti-breast cancer agents.
authors.affiliation: Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India; Department of Chemistry, Yashwantrao Chavan Mahavidyalaya, Tuljapur, Dist-Osmanabad 413 601, Maharashtra, India.
authors.forename: Pravin S
authors.initials: PS
authors.lastname: Bhale
authors.affiliation: Department of Chemistry, A.S.P. College, Devrukh, Dist-Ratnagiri 415 804, Maharashtra, India. Electronic address: hemantchavan.sus@rediffmail.com.
authors.forename: Hemant V
authors.initials: HV
authors.lastname: Chavan
authors.affiliation: Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India.
authors.forename: Sakharam B
authors.initials: SB
authors.lastname: Dongare
authors.affiliation: Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India.
authors.forename: Sadanand N
authors.initials: SN
authors.lastname: Shringare
authors.affiliation: Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India.
authors.forename: Yoginath B
authors.initials: YB
authors.lastname: Mule
authors.affiliation: Polymer and Advanced Materials Laboratory, National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Samadhan S
authors.initials: SS
authors.lastname: Nagane
authors.affiliation: Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India.
authors.forename: Babasaheb P
authors.initials: BP
authors.lastname: Bandgar
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004008:Diclofenac / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004527:Egg Proteins / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D061986:MCF-7 Cells; D009569:Nitric Oxide / Q000378:metabolism; D011489:Protein Denaturation; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014709:Vero Cells
chemical_list: D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D047188:Chalcones; D004527:Egg Proteins; D016166:Free Radical Scavengers; D007211:Indoles; D013481:Superoxides; D004008:Diclofenac; D009569:Nitric Oxide; D004317:Doxorubicin
keywords: Anti-inflammatory; Antioxidant; Cytotoxicity; Extended conjugation; Indole chalcones