Browsing by Author "Pavan Srivastava"

Now showing 1 - 3 of 3

Biphenyl-3-oxo-1,2,4-triazine linked piperazine derivatives as potential cholinesterase inhibitors with anti-oxidant property to improve the learning and memory
(Academic Press Inc., 2019) Prabhash Nath Tripathi; Pavan Srivastava; Piyoosh Sharma; Manish Kumar Tripathi; Ankit Seth; Avanish Tripathi; Sachchida Nand Rai; Surya Pratap Singh; Sushant K. Shrivastava
A series of novel piperazine tethered biphenyl-3-oxo-1,2,4-triazine derivatives were designed, and synthesized. Amongst the synthesized analogs, compound 6g showed significant non-competitive inhibitory potential against acetylcholinesterase (AChE, IC 50 ; 0.2 ± 0.01 μM) compared to standard donepezil (AChE, IC 50 : 0.1 ± 0.002 μM). Compound 6g also exhibited significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE (22.22 ± 1.11%) and showed good CNS permeability in PAMPA-BBB assay (P e (exp) , 6.93 ± 0.46). The in vivo behavioral studies of compound 6g indicated significant improvement in cognitive dysfunctions against scopolamine-induced amnesia mouse models. Further, ex vivo studies showed a significant AChE inhibition and reversal of the scopolamine-induced oxidative stress by compound 6g. Moreover, molecular docking and dynamics simulations of compound 6g showed a consensual binding affinity and active site interactions with the PAS and active catalytic site (CAS) residues of AChE. © 2018 Elsevier Inc.
Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease
(Academic Press Inc., 2019) Sushant K. Shrivastava; Saurabh K. Sinha; Pavan Srivastava; Prabhash N. Tripathi; Piyoosh Sharma; Manish K. Tripathi; Avanish Tripathi; Priyanka K. Choubey; Digambar K. Waiker; Lalit M. Aggarwal; Manish Dixit; Subhash C. Kheruka; Sanjay Gambhir; Sharmila Shankar; Rakesh K. Srivastava
Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE. © 2018 Elsevier Inc.
Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory
(Elsevier Masson SAS, 2019) Pavan Srivastava; Prabhash Nath Tripathi; Piyoosh Sharma; Sachchida Nand Rai; Surya Pratap Singh; Rakesh K. Srivastava; Sharmila Shankar; Sushant K. Shrivastava
Based on the Gaussian-based quantitative structure-activity relationship (QSAR) and virtual screening (VS) processes, some promising acetylcholinesterase inhibitors (AChEIs) having antioxidant potential were designed synthesized, characterized, and evaluated for their ability to enhance learning and memory. The synthesized phenyl benzoxazole derivatives exhibited significant antioxidant potential and AChE inhibitory activity, whereas the antioxidant potential of compound 34 (49.6%) was observed significantly better than standard donepezil (<10%) and parallel to ascorbic acid (56.6%). Enzyme kinetics study of most potent compound 34 (AChE IC50 = 0.363 ± 0.017 μM; Ki = 0.19 ± 0.03 μM) revealed the true nature and competitive type of inhibition on AChE. The compound 34 was further assessed for in vivo and ex vivo studies and the results showed the significant reversal of cognitive deficits and antioxidant potential at the dose of 5 mg/kg comparable to standard drug donepezil. © 2018 Elsevier Masson SAS