title: Synthesis and mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling.
abstract: A series of anilinonicotinyl linked pyrazolo[1,5-a]pyrimidine conjugates (6a-x) were synthesized and evaluated for their antiproliferative activity. Some of these conjugates exhibited promising cytotoxic effects in the MCF-7 cell line and among these 6a and 6c exhibited significant effects, apart from G2/M cell cycle arrest. Interestingly they showed profound effects on cyclin D1, Bcl-2 and survivin proteins that regulate breast cancer cell proliferation. Moreover, ER alpha protein expression was studied to understand regulatory role of these conjugates on estrogen activity in estrogen positive breast cancer cells like MCF-7 and compounds 6a and 6c reduced their activity.
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Shaikh
authors.initials: S
authors.lastname: Faazil
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: S M Ali
authors.initials: SM
authors.lastname: Hussaini
authors.affiliation: Chemical Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: M
authors.initials: M
authors.lastname: Balakrishna
authors.affiliation: Chemical Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Nibedita
authors.initials: N
authors.lastname: Patel
authors.affiliation: Chemical Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.affiliation: Chemical Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C000612708:2-anilinonicotinyl-pyrazolo(1,5-a)pyrimidine; D000970:Antineoplastic Agents; D004967:Estrogens; D011743:Pyrimidines; D009538:Nicotine
keywords: Bcl-2; Cell cycle; Cyclin D1; Estrogen receptors; Pyrazolopyrimidine