MAY 2014 ARTICLE LIST >>
PharmaTutor (May- 2014)
ISSN: 2347 - 7881
Received On: 07/03/2014; Accepted On: 15/03/2014; Published On: 01/05/2014
Author: Vinit Raj*, Amit Rai, Jitendra Kumar Rawat
Department of Pharmaceutical Sciences,
Babasaheb Bhimrao Ambedkar University (A Central University),
Vidya Vihar, Raebreli Road, Lucknow, Uttar Pradesh, India
raj.vinit24@gmail.com
ABSTRACT:
A series of novel 1, 3, 4-thiadiazole derivatives were designed keeping in view the structural requirement of pharmacophore and Quantitative structure activity relationship (QSAR) and evaluated in silico anticonvulsant activity. Docking procedures allow virtually screening a database of compounds and predict the strongest binder based on various scoring functions. In the docking study, the most active compounds of the series were, VR 2, VR 3 and VR 4 exhibited good binding properties. Result reveals that the protein-ligand interaction energy of derivatives VR 2, VR 3 and VR 4 were -7.08 kcal/mol, -6.64 kcal/mol and -7.42 kcal/mol respectively, which is slightly higher than the standard anticonvulsant phenytoin drug as -6.03 kcal/mol, so that the derivatives have satisfactory affinity with established convulsant receptor namely Na/H exchanger. A computational study was also carried out including prediction of pharmacokinetic properties, toxicity and bioactivity studies. The percentage of absorption (%ABS) was calculatedand observed that all titled compounds exhibited a better %ABS ranging 92.66, 85.81, 90.07 and 86.98, respectively and compared than standard Phenytoin drug as %ABS 88.92. Although VR 1 had slightly lesser protein affinity, its other pharmacological parameters were same like other screened compounds. The above observation suggested that these compounds would serve as better lead compound for anticonvulsant screening for future drug design perspective.
How to cite this article: V Raj, A Rai, JK Rawat; In Silico Design and Computational Study of Novel 1, 3, 4-Thiadiazole Derivatives as Potential Affinity with NA/H Exchanger Receptor for Anticonvulsant Activity; PharmaTutor; 2014; 2(5); 113-119
[ABSTRACT WITH CITATION] [VIEW AS HTML]
REFERENCES:
1.McNamara OJ:Drugs effectivein the therapy of the Epilepsy. in: Hardman JG, Gilman(Eds) LC. The Pharmacological basis of therapeutical. McGraw-Hill, New York 2001: 521-548.
2.Loscher W: New visions in the pharmacology of anticonvulsion. Eur.J. Pharmacol.1998: 342,1e13.
3.ChangBS, LowensteinDH:Epilepsy. N. Engl. J. Med2003, 349 (13):1257-1266.
4.Schmidt D, Stavem K.:Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: a review of controlled studies. Epilepsia2009, 50:1301.
5.Perucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on, topiramate zonisamide and tiagabine. Clin Pharmacokinet1996, 31:29–46.
6.Zhaiwei Lin, Pankaja K Kadab.Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents, Med. Res. Rev1997,17(6): 537-572.
7.Pandeya SN, Raja AS, Stables JP.Synthesis of isatin semicarbazones as novel anticonvulsants-role of hydrogen bonding,J. Pharm Pharm Sci2002,5(3): 266-71.
8.Can ÖD, Altlntop MD, Özkay ÜD, Üçel UI, Ruer BD, Kaplanclkl ZA. Synthesis of Thiadiazole Derivatives Bearing Hydrazone Moieties and Evaluation of Their Pharmacological Effects on Anxiety, Depression, and Nociception Parameters in Mice. Arch Pharm Res2012, 35(4): 659-669.
9.Demirbas N, Karaoglu SA, Sancak K..Synthesis and antimicrobial activities of some new 1- (5-phenylamino-[1, 3, 4]thiadiazole-2-yl)methyl-5-oxo-[1, 2, 4]triazole and 1-(4-phenyl-5-thioxo-[1, 2, 4] triazole-3-yl)methyl-5-oxo-[1, 2, 4]triazole derivatives, Eur J Med Chem2004, 39: 793-804.
10.Karegoudar P, Jagdeesh Prasad D, Ashok M, Mahalinga M, Poojary B, Shivarama Holla B.Synthesis, Antimicrobial And Anti-Inflammatory Activities Of Some 1, 2, 4-Triazolo[3, 4-B][1, 3, 4]Thiadiazoles And 1, 2, 4-Triazolo [3, 4-B][1, 3, 4] Thiadiazines Bearing Trichlorophenyl Moietyeuropean. Journal of Medicinal Chemistry2008, 43: 808-815.
11.Chou Y, Lais Y, Pan L, Jow M, Chen W, Guh H. Investigation of anticancer mechanisms of thiadiazole-based compound in human non-small cell lung cancer A 549 cells, Biochemist. Pharmacology 2003, 66: 115-124.
12.Cleici F, Pocar D, Guido M, Loch A, Perlini V, Brufani M. Synthesis of 2-amino-5-sulfanyl-1, 3, 4-thiadiazole derivatives and evaluation of their antidepressant and anxiolytic activity, J Med Chem2001, 44 (6): 931-936.
13.Martinez A, Alonso D, Castro A, Aran J, Cardelus I, Banos E. Synthesis and Potential muscarinic receptor binding and antioxidant properties of 3-(thiadiazolyl) pyridine 1-oxide compounds. Arch Pharm1999, 332:191-194.
14.Mohammad Y, Riaz AK, Khan M, Ahmed B.An Interactive Human Carbonic Anhydrase-II (hCA-II)Receptor–Pharmacophore Molecular Model & Anti-Convulsant Activity of the Designed and Synthesized 5-Amino-1,3,4-Thiadiazole-2-Thiol Conjugated Imine Derivatives, Chem Biol Drug Des2013, 81: 666–673.
15.Shankar GA, Kallanagouda R, Alagawadi Pranali V, Sonkusare Sagar M, Chaudhary Dilip H, Dadwe Amol S Shah. Novel imidazo [2, 1-b][1, 3, 4] thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents, Bioorganic & Medicinal Chemistry Letters2012, 22: 1917–1921.
16.Oruc E, Rollas S, Kandemirli F, Shvets N, Dimoglo A. 1, 3, 4-thiadiazole derivatives, synthesis, structure elucidation and structure antituberculosis activity relationship investigation, J Med Chem2004, 47: 6760-6767.
17.Srivastava V, Kumar A.Molecular docking studies on DMDP derivatives as human DHFR inhibitors, Bioinformation2008, 3(4): 180-188.
18.Molinspiration Cheminformatics, Bratislava, Slovak Republic, Available from: molinspiration.com/services/properties.html[accessed 16.08.2010].
19.Zhao Y, Abraham MH, Lee J, Hersey A, Luscombe NC, Beck G, Sherborne BI.Rate-limited steps of human oral absorption and QSAR studies. Pharm. Res2002, 19, 1446–1456.
.png)
