title: Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents.
abstract: In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski 'Rule of five' were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis (INHR-TB) with minimum inhibitory concentrations (MICs) 0.78μM and 1.52 μM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4-8 μg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8-16 μg/mL less active than standard drug fluconazole.
authors.affiliation: New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar, Rajasthan 301 030, India. jawedpharma@gmail.com
authors.forename: Mohamed Jawed
authors.initials: MJ
authors.lastname: Ahsan
authors.forename: Jeyabalan Govinda
authors.initials: JG
authors.lastname: Samy
authors.forename: Habibullah
authors.initials: H
authors.lastname: Khalilullah
authors.forename: Md Shivli
authors.initials: MS
authors.lastname: Nomani
authors.forename: Pankaj
authors.initials: P
authors.lastname: Saraswat
authors.forename: Ramakant
authors.initials: R
authors.lastname: Gaur
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D010069:Oxadiazoles