Design, synthesis and evaluation of diarylpiperazine derivatives as potent anti-tubercular agents.
Molecular hybridization is an emerging approach to design novel ligands by combination of two or more pharmacophoric subunits of known bioactive compounds. In the present study, we have designed a novel series of diarylpiperazine analogues, synthesized, characterized using FTIR, (1)H NMR, Mass, Elemental analysis and evaluated their in-vitro anti-tubercular activity. Among the reported sixteen diarylpiperazines, eleven analogues exhibited significant anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC values below 6.25 μg/mL and good selectivity index. Structure activity relationship studies concluded that, ortho-para directing group (except para chloro) substitution on ortho and para position of piperazine attached phenyl ring favored anti-tubercular activity.
Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, 333031, India.
Ashok
A
Penta
Institute for Tuberculosis Research, MC-964 College of Pharmacy, University of Illino's at Chicago, 833 S. Wood St, Chicago, IL, 60621-7231, USA.
Scott
S
Franzblau
Institute for Tuberculosis Research, MC-964 College of Pharmacy, University of Illino's at Chicago, 833 S. Wood St, Chicago, IL, 60621-7231, USA.
Baojie
B
Wan
Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, 333031, India. Electronic address: murugesan@pilani.bits-pilani.ac.in.
Sankaranarayanan
S
Murugesan
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000995:Antitubercular Agents; D010879:Piperazines
Mycobacterium tuberculosis; Piperazine; β-carboline