Hira KHALID, Aziz Ur REHMAN, Muhammad Athar ABBASI

Synthesis, biological evaluation, and molecular docking of N'-(Aryl/alkylsulfonyl)-1-(phenylsulfonyl) piperidine-4-carbohydrazide derivatives

A series of new N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazide derivatives were synthesized. Starting from ethyl piperidine-4-carboxylate (a), first ethyl 1-(phenylsulfonyl)piperidine-4-carboxylate (1), second 1-(phenylsulfonyl)piperidine-4-carbohydrazide (2), and finally N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazides (4a--n) were synthesized by reacting 2 with alkyl/aryl sulfonyl chlorides (3a--n). The structures of the synthesized compounds were characterized by IR, 1H-NMR, and EI-MS spectra and all were screened in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Molecular docking was accomplished for these compounds to examine their binding interactions with AChE and BChE human proteins. The strategy we applied for this purpose was a direct receptor-based approach. The binding modes of the inhibitors under study were determined using an automated docking program (AutoDock) and were compared with antienzymatic IC50 values. Both studies confirmed the potential of compounds as excellent inhibitors for AChE and BChE.

Anahtar Kelimeler:

Ethyl piperidine-4-carboxylate, benzenesulfonyl chloride, piperidine-4-carbohydrazide, enzyme inhibition, molecular docking, spectral analysis, AChE/BChE inhibitors

Synthesis, biological evaluation, and molecular docking of N′ -(Aryl/alkylsulfonyl)-1-(phenylsulfonyl) piperidine-4-carbohydrazide derivatives

Keywords:

Ethyl piperidine-4-carboxylate, benzenesulfonyl chloride, piperidine-4-carbohydrazide, enzyme inhibition, molecular docking, spectral analysis, AChE/BChE inhibitors,

PDF

___

Massoulie, J.; Pezzementi, L.; Bon, S.; Krejci, E.; Valette, F. M. Prog. Neurobiol. 1993, 41, 31–91.
Chatonnet, A.; Lockridge, O. Biochem. J. 1989, 260, 625–634.
C ¸ oku˘ gra¸s, N. A. Turk. J. Biochem. 2003, 28, 54–61.
Sussman, L. J.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.; Toker, L.; Silman, I. Protein Sci. 1991, 253, 872–878.
Gilman, A. G.; Rall, T. W.; Nies, A.; Taylor, P. In The Pharmacological Basis of Therapeutics; Eds. Pergamon, New York 1990, pp. 131–149.
Hallak, M.; Giacobini, E. Neuropharmacology 1989, 28, 199–206.
Scarpini, E.; Scheltens, P.; Feldman, H. Lancet Neurol. 2003, 2, 539–547.
Perry, E. K.; Tomlinson, B. E.; Blessed, G.; Bergman, K.; Gibson, P. H.; Perry, R. H. Brit. Med. J. 1978, 25, 1457–1459.
Holzgrabe, U.; Kapkova, P.; Alptuzun, V.; Scheiber, J.; Kugelmann, E. Expert. Opin. Ther. Targets 2007, 11, 161–179.
Butini, S.; Campiani, G.; Borriello, M.; Gemma, S.; Panico, A.; Persico, M.; Catalanotti, B.; Ros, S.; Brindisi, M.; Agnusdei, M.; et al. J. Med. Chem. 2008, 51, 3154–3170.
Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V. Biochem. Pharmacol. 2003, 65, 407–416.
Shafferman, A.; Velan, B.; Ordentlich, A.; Kronman, C.; Grosfeld, H.; Leitner, M.; Flashner, Y.; Cohen, S.; Barak, D.; Ariel, N. EMBO J. 1992, 11, 3561–3568.
Changeux, J. P. Mol. Pharmacol. 1966, 2, 369–392.
Cochard, P.; Coltey, P. Dev. Biol. 1983, 98, 221–238.
Chatonnet, A.; Lockridge, O. Biochem. J. 1989, 260, 625–634.
Sikorav, J. L.; Krejci, E.; Massoulie, J. EMBO J. 1987, 6, 1865–1873.
Solis, A.; Nava, A.; Perez, H. I.; Manjarrez, N.; Luna, H.; Cassani, J. J. Mex. Chem. Soc. 2008, 52, 181–184. Khalid, H. Aziz-ur-Rehman; Abbasi, M. A.; Khan, K. M. Int. J. Pharm. Pharm. Sci. 2012, 4, 443–448.
Aziz-ur-Rehman; Nafeesa, K.; Abbasi, M. A.; Khalid, H.; Khan, K. M.; Ashraf, M.; Ahmad, I.; Ejaz, S. A. Asian. J. Pharm. Hea. Sci. 2012, 2, 370–376.
Aziz-ur-Rehman; Siddiqui, S. Z.; Abbas, N.; Abbasi, M. A.; Khan, K. M.; Shahid, M.; Mahmood, Y.; Akhtar, N. M.; Lajis, N. H. Int. J. Pharm. Pharm. Sci. 2012, 4, 676–680.
Ellman, G. L.; Courtney, K. D.; Andres, V.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88–95.
Kryger, G.; Harel, M.; Giles, K.; Toker, L.; Velan, B.; Lazar, A.; Kronman, C.; Barak, D.; Ariel, N.; Shafferman, A.; et al. Acta. Crystallogr. D. 2000, 56, 1385–1394.
Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. J. Comput. Chem. 2004, 25, 1605–1612.
Humphrey, W.; Dalke, A.; Schulten, K. J. Mol. Graphics 1996, 14, 33–38.
Allouche, A. R. J. Comput. Chem. 2010, 32, 174–182.
Stewart, J. P. J. Mol. Model. 2007, 13, 1173–1213.
Trott, O.; Olson, A. J. J. Comput. Chem. 2010, 31, 455–461.
Deng, X; Mani, N. S. Green Chem. 2006, 8, 835–838.
Jafarpour, M; Rezaeifard, A; Golshani, T. J. Phosphorous, Sulfur and Silicon. 2011, 186, 140–148.
Aziz-ur-Rehman; Afroz, S; Abbasi, M. A; Tanveer, W; Khan, K. M; Asraf, M; Afzal, I; Ambreen. Pak. J. Pharm. Sci. 2012, 25, 809–814.
Aziz-ur-Rehman; Rasool, S; Abbasi, M. A; Khan, K. M; Asraf, M.; Afzal, I. Asian J. Phram. Bio. Res. 2012, 2, 100–105.
Aziz-ur-Rehman; Awais-ur-Rehman; Abbasi, M. A; Khalid, H; Khan, K. M; Dar, P. Asian J. Pharm. Hea. Sci. 2012, 2, 384–389.