title: Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.
abstract: A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25μM against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU-145 cell line and Gram negative bacterial strains.
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506004, Telangana, India.
authors.forename: Krishnaiah
authors.initials: K
authors.lastname: Vaarla
authors.affiliation: Department of Biotechnology, National Institute of Technology, Warangal 506004, Telangana, India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Kesharwani
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana 500607, India.
authors.forename: Karnewar
authors.initials: K
authors.lastname: Santosh
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506004, Telangana, India. Electronic address: rajeswarnitw@gmail.com.
authors.forename: Rajeswar Rao
authors.initials: RR
authors.lastname: Vedula
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana 500607, India.
authors.forename: Srigiridhar
authors.initials: S
authors.lastname: Kotamraju
authors.affiliation: Department of Microbiology, Kakatiya University, Warangal, Telangana, India.
authors.forename: Murali Krishna
authors.initials: MK
authors.lastname: Toopurani
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065637:Cytochrome P-450 CYP2A6 / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D008861:Microsomes / Q000378:metabolism; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D003374:Coumarins; D011720:Pyrazoles; C031280:pyrazole; C030123:coumarin; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6
keywords: 3-(2-Bromoacetyl)coumarins; Anti cancer activity; Docking; Thiazolyl-pyrazoles; Thiosemicarbazide; Vilsmeier–Haack formylation