Design, synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides

作者：Kumari Shikha; Mishra Chandra Bhushan; Idrees Danish; Prakash Amresh; Yadav Rajesh; Hassan Md Imtaiyaz^*; Tiwari Manisha^*

来源：Molecular Diversity, 2017, 21(1): 163-174.

DOI：10.1007/s11030-016-9714-7

• CAII inhibitors
• Docking
• Drug design and discovery
• Piperazine-hydrazine carboxamide derivatives
• MD simulation

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 values between against CAI and against CAII. Compound 3g was the most active inhibitor, with an value of 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 () 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.

• 出版日期2017-2