title: Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis.
abstract: A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.8 μg/mL against different bacterial strains. Compound 5r also showed good antifungal and anti-biofilm activities against the tested panel of various fungal and bacterial strains. Compound 5r when treated on mature biofilms of S. aureus strain MLS16, showed increased levels of intracellular ROS accumulation suggesting its contribution to the bactericidal activity. All the compounds were also screened for anticancer activity against a panel of four human cancer cell lines. Based on these studies, compounds 5c, 5d, 5r and 7f were considered as promising and exhibited significant cytotoxicity with IC50values of <15 μM. The biological activity data was further validated by molecular modeling and CoMFA studies.
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Jitender Dev
authors.initials: JD
authors.lastname: G
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: K
authors.initials: K
authors.lastname: Ratnakar Reddy
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: R
authors.initials: R
authors.lastname: Naresh Kumar
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Department of Chemistry, Osmania University, Tarnaka, Hyderabad, 500007, India.
authors.forename: N
authors.initials: N
authors.lastname: Ravikumar
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: D
authors.initials: D
authors.lastname: Krishna Swaroop
authors.affiliation: Department of Chemistry, Osmania University, Tarnaka, Hyderabad, 500007, India.
authors.forename: P
authors.initials: P
authors.lastname: Ranjithreddy
authors.affiliation: Bioinformatics Division, Osmania University, Hyderabad, 500007, India.
authors.forename: G
authors.initials: G
authors.lastname: Shravan Kumar
authors.affiliation: Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Jagadeesh B
authors.initials: JB
authors.lastname: Nanubolu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: C
authors.initials: C
authors.lastname: Ganesh Kumar
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India. Electronic address: narsaiah@iict.res.in.
authors.forename: B
authors.initials: B
authors.lastname: Narsaiah
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D018441:Biofilms / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D011720:Pyrazoles; D011804:Quinolines; C037219:quinoline
keywords: Anticancer activity; Antimicrobial activity; Chlorination; Pyrazole fused quinoline; Quinoline 2(1H) one