title: Regioselective synthesis and biological studies of novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives as potential antiproliferative agents.
abstract: Pyrazole moiety represents an important category of heterocyclic compound in pharmaceutical and medicinal chemistry. The novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives were synthesized with complementary regioselectivity. The chemical structures were confirmed by IR,1H NMR,13C NMR, and mass spectral analysis. The chemical entities were screened in various cancer cell lines to assess their cell viability activity. Results showed that the compound 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl) pyridine (5d) possessed maximum cytotoxic effect against breast cancer and leukemic cells. The cytotoxicity was confirmed by live-dead cell assay and cell cycle analysis. Mitochondrial membrane potential, Annexin V-FITC staining, DNA fragmentation, Hoechst staining, and western blot assays revealed the ability of compound 5d to induce cell death by activating apoptosis in cancer cells. Thus, the present study demonstrates that compound 5d could be an attractive chemical entity for the development of small molecule inhibitors for treatment of leukemia and breast cancer.
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, 570006, India.
authors.forename: Hanumappa
authors.initials: H
authors.lastname: Ananda
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, 570006, India.
authors.forename: Kothanahally S
authors.initials: KS
authors.lastname: Sharath Kumar
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Mayilaadumveettil
authors.initials: M
authors.lastname: Nishana
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, 570006, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, 570006, India.
authors.forename: Raghava
authors.initials: R
authors.lastname: Byregowda
authors.affiliation: Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore, 560 100, India.
authors.forename: Bibha
authors.initials: B
authors.lastname: Choudhary
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India. sathees@biochem.iisc.ernet.in.
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, 570006, India. rangappaks@chemistry.uni-mysore.ac.in.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D011720:Pyrazoles
keywords: Apoptosis; Breast cancer; Dithioesters; MCF7; Pyrazole; Regioselectivity