title: Design, synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides.
abstract: A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazinecarboxamide derivatives has been successfully designed and synthesized to evaluate their potential as carbonic anhydrase (CA) inhibitors. The inhibitory potential of synthesized compounds against human CAI and CAII was evaluated. Compounds 3a-n exhibited [Formula: see text] values between [Formula: see text] against CAI and [Formula: see text] against CAII. Compound 3g was the most active inhibitor, with an [Formula: see text] value of [Formula: see text] against CAII. Molecular docking studies of compound 3g with CAII showed this compound fits nicely in the active site of CAII and it interacts with the zinc ion ([Formula: see text]) along with three histidine residues in the active site. Molecular dynamics simulation studies of compound 3g complexed with CAII also showed essential interactions which were maintained up to 40 ns of simulation. In vivo sub-acute toxicity study using 3g (300 mg/kg) was found non-toxic in adult Wistar rats.
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, New Delhi, Delhi, 110007, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, New Delhi, Delhi, 110007, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
authors.forename: Danish
authors.initials: D
authors.lastname: Idrees
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
authors.forename: Amresh
authors.initials: A
authors.lastname: Prakash
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, New Delhi, Delhi, 110007, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. mihassan@jmi.ac.in.
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, New Delhi, Delhi, 110007, India. mtiwari07@gmail.com.
authors.forename: Manisha
authors.initials: M
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D006834:Hydrazines; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: CAII inhibitors; Docking; Drug design and discovery; MD simulation; Piperazine-hydrazine carboxamide derivatives