title: Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents.
abstract: A series of novel 1,3,5-trisubstituted pyrazolines derivatives have been synthesized from chalcones and nicotinic acid hydrazide in two steps. In first step, chalcones were prepared by treatment of 4-hydroxy acetophenone with different substituted benzaldehyde by Claisen-Schimidt Condensation. In second step, various pyrazoline derivatives were prepared by reflux reaction of chalcones with nicotinic acid hydrazide in ethanolic solution. Compounds were confirmed by elemental analyses, IR,1H NMR and13C NMR spectral data and were evaluated for antimalarial and antibacterial activity. Compounds 5n (IC50=0.022μM for MRC-2 and IC50=0.192μM for RKL-9) displayed better antiplasmodial activity than the chloroquine (CQ) against chloroquine-sensitive (MRC-2) and chloroquine-resistant (RKL-9) P. falciparum strains. The in vitro cytotoxicity study conducted on the human HepG2 cell line (>30μM) and selectivity index (100-220) indicate that this series presents an interesting selective antiplasmodial profile. Further, in vitro heme crystallization inhibition assay showed compound 5e inhibited formation of β-hematin more efficiently than CQ. In addition, antibacterial and antifungal evaluations were conducted, compounds 5c, 5i and 5j displayed better antibacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa than ciproafloxacin. Antifungal activity of compound 5l against A. niger (MIC-3.25μg/ml) and C. albicans (MIC-6.5μg/ml) was found to be better than the standard drug fluconazole.
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar, MP, India.
authors.forename: Vikash K
authors.initials: VK
authors.lastname: Mishra
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar, MP, India.
authors.forename: Mitali
authors.initials: M
authors.lastname: Mishra
authors.affiliation: SVN Institute of Pharmaceutical Sciences, SVN University, Sagar, MP, India.
authors.forename: Varsha
authors.initials: V
authors.lastname: Kashaw
authors.affiliation: Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar, MP, India; Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA. Electronic address: http://www.dhsgsu.ac.in.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Kashaw
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D066244:Proton Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D011720:Pyrazoles
keywords: Antifungal; Antimalarial; Antimicrobial; Claisen-Schmidt condensation; Cytotoxicity assay; Heme crystallization inhibition assay; Pyrazolines