Synthesis, in silico Studies, and Anticonvulsant Activity of 1,3,4-Oxadiazole Derivatives
DOI:
https://doi.org/10.48048/tis.2021.701Keywords:
1,3,4-oxadiazole, Anticonvulsant activity, GABAA receptor, Molecular dockingAbstract
The title compounds 1,3,4-oxadiazole derivatives (C1-5) were synthesized by the cyclization of 4-hydroxy benzhydrazide (1) with various substituted aromatic aldehydes (2) in the presence of ceric ammonium nitrate. The structures of the newly synthesized compounds were established based on FT-IR, 1H-NMR, and Mass spectral data. In silico analysis was carried out using the Schrodinger 2018-3 suite device Maestro and docked to the binding site of the Human GABAA receptor (PDB ID:4COF). The toxicity of the compounds was predicted using the LAZAR (Lazy structure-activity relationship) program. The invivo anticonvulsant study was performed by means of a maximal electroshock test and pentylenetetrazole (PTZ)-induced seizures. Compounds C4&C5 showed the highest docking score of −5.676 and −5.277, respectively, and compounds C4&C5 showed the most increased in vivo anticonvulsant activity when compared with the reference drugs in both the PTZ and MES test methods.
HIGHLIGHTS
- A new series of 1,3,4-oxadiazoles (C1-C5) were synthesized by reacting aromatic aldehydes and 4-hydroxy benzhydrazide using cerric ammonium nitrate as (CAT) catalyst and characterized by spectral data
- All the new compounds were subjected for In-silico analysis and docked to Human GABAA receptor (PDB ID:4COF)
- In-vivo anticonvulsant activity was carried out for all the new compounds by using maximal electroshock (MES) and pentylenetetrazole (PTZ) models
- Some of the tested compounds C4&C5 displayed promising anticonvulsant activity
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S Bala, S Kamboj and A Kumar. Heterocyclic 1,3,4-oxadiazole compounds with diverse biological activities: A comprehensive review. J. Pharm. Res. 2010; 3, 2993-7.
E Palaska, G Şahin, P Kelicen, NT Durlu and G Altinok. Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones. IL Farmaco 2002; 57, 101-7.
AMME Omar and OM Aboulwafa. Synthesis and anticonvulsant properties of a novel series of 2‐substituted amino‐5‐aryl‐1, 3, 4‐oxadiazole derivatives. J. Hetero. Chem. 1984; 21, 1415-28.
G Şahin, EPalaska, M Ekizoğlu and M Özalp. Synthesis and antimicrobial activity of some 1,3,4-oxadiazole derivatives. IL Farmaco 2002; 57,539-42.
SV Bhandari, KG Bothara, MK Raut, AA Patil, AP Sarkate and VJ Mokale. Design, synthesis and evaluation of antiinflammatory, analgesic and ulcerogenicity studies of novel S-substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of diclofenac acid as nonulcerogenic derivatives. Bio. Med. Chem. 2008; 16, 1822-31.
HP Shah, B Shah, JJ Bhatt, NC Desai, PB Trivedi and NK Undavia. Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles as potential antimicrobial, anticancer and anti-HIV agents. ChemInform 1998; 29, 199839132.
AO Maslat, M Abussaud, H Tashtoush and M AL-Talib. Synthesis, antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives. Pol. J. Pharmacol. 2002; 54, 55-9.
AS Aboraia, HM Abdel-Rahman, NM Mahfouz and MA El-Gendy. Novel 5-(2-hydroxyphenyl)-3-substituted-2, 3-dihydro-1, 3, 4-oxadiazole-2-thione derivatives: Promising anticancer agents. Bio. Med. Chem. 2006; 14, 1236-46.
AA Santilli and RL Morris. Synthesis of 3‐arylsulfonylmethyl‐1,2,4‐oxadiazole‐5‐carboxylic acid derivatives. J. Hetero. Chem. 1979; 16, 1197-200.
J Roh, GKarabanovich, H Vlčková, A Carazo, J Němeček, P Sychra, L Valášková, O Pavliš, J Stolaříková, V Klimešová and K Vávrová. Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazoleantitubercular agents. Bio. Med. Chem. 2017; 5, 5468-76.
D Dewangan, A Pandey, T Sivakumar, R Rajavel and RD Dubey. Synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazole and its analgesic, anti-inflammatory, anti-bacterial and anti-tubercular activity. Int. J. Chem. Tech. Res. 2010; 2, 1397-412.
SU Haque, H Welch, M Dashwood, B Ramesh and M Loizidou. Efficacy of zibotentan in colorectal cancer-response. Mol. Cancer Thera. 2014; 13, 674-80.
NB Patel, JN Patel, AC Purohit, VM Patel, DP Rajani, R Moo-Puc, JC Lopez-Cedillo, B Nogueda-Torres and G Rivera. In vitro and in vivoassessment of newer quinoxaline-oxadiazole hybrids as antimicrobial and antiprotozoal agents. Int. J. Antimicrob. Agents 2017; 50, 413-8.
V Summa, A Petrocchi, F Bonelli, B Crescenzi, M Donghi, M Ferrara, F Fiore, C Gardelli, OG Paz, DJ Hazuda, P Jones, O Kinzel, R Laufer, E Monteagudo, E Muraglia, E Nizi, F Orvieto, P Pace, G Pescatore, R Scarpelli, K Stillmock, MV Witmer and M Rowley. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem. 2008; 51, 5843-55.
NC Desai, N Bhatt, H Somani and A Trivedi. Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles. Eur. J. Med. Chem. 2013; 67, 54-9.
ML Cohen, KS Wiley and AS Landry. In vitro comparison of the pre-and postsynaptic alpha adrenergic receptor blocking properties of prazosin and tiodazosin (BL5111). Clin. Exp. Hypertens. 1980; 2, 1067-82.
NC Desai, GMKotadiya, ARTrivedi, VMKhedkar and PCJha. Design, synthesis, and biological evaluation of novel fluorinated pyrazole encompassing pyridyl 1,3,4-oxadiazole motifs. Med. Chem. Res. 2016; 25, 2698-717.
PP Roy, S Bajaj, TK Maity and J Singh. Synthesis and evaluation of anticancer activity of 1,3,4-oxadiazole derivatives against ehrlich ascites carcinoma bearing mice and their correlation with histopathology of liver. receptor. Ind. J. Pharm. Edu. Res. 2017; 51, 260-69.
A Rigo and M Lagrenee. A simple and efficient procedure for synthesis of optically active 1,3,4-oxadiazole derivatives containing Lamino acid moieties. J. Het. Chem. 1999; 36, 1029-32.
R Kumar, T Singh, H Singh, S Jain and RK Roy. Design, synthesis and anticonvulsant activity of some new 6, 8-halo-substituted-2h-[1,2,4] triazino [5,6-b] indole-3 (5h)-one/-thione and 6, 8-halo-substituted 5-methyl-2h-[1,2,4] triazino [5,6-b] indol-3 (5h)-one/-thione. Exp. Clin. Sci. J. 2014; 13, 225-32.
I D’AndreaMeira, TTRomão, HJPD Prado, LTKrüger, MEPPires and PODConceição. Ketogenic diet and epilepsy: What we know so far. Front. Neurosci.2019;13, 5.
MM Goldenberg. Overview of drugs used for epilepsy and seizures: Etiology, diagnosis, and treatment. Pharm. Thera. 2010; 35, 392-400.
HA Abuelizz, RE Dib, M Marzouk, EH Anouar, YA Maklad, HN Attia and R Al-Salahi. Molecular docking and anticonvulsant activity of newly synthesized quinazoline derivatives. Molecules 2017; 22, 1094-80.
PS Miller and AR Aricescu. Crystal structure of a human GABAA receptor. Nature 2014; 512, 270-5.
TM DeLorey and RW Olsen. GABA and epileptogenesis: Comparing gabrb3 gene-deficient mice with Angelman syndrome in man. Epilepsy Res. 1999; 36, 123-32.
HJ Lankau, K Unverferth, C Grunwald, H Hartenhauer, K Heinecke, K Bernöster, R Dost, U Egerland and C Rundfeldt. New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity. Euro. J. Med. Chem. 2007; 42, 873-9.
BF Gatphoh, BC Revanasiddappa, MV Kumar and H Kumar. Synthesis, anti-arthritic and antioxidant activities of novel 1,3,4-oxadiazole derivatives. Synthesis, anti-arthritic and antioxidant activities of novel 1,3,4-oxadiazole derivatives. Indian Drugs 2018; 55, 18-23.
M Tanaka, RW Olsen, MT Medina, E Schwartz, ME Alonso, RM Duron, R Castro-Ortega, IE Martinez-Juarez, IPascual-Castroviejo, J Machado-Salas, R Silva, JN Bailey, D Bai, A Ochoa, A Jara-Prado, G Pineda, RL Macdonald and AV Delgado-Escueta. Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. Am. J. Hum. Genet. 2008; 82, 1249-61.
KN Gurba, CC Hernandez, N Hu and RL Macdonald. GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating. J. Bio. Chem. 2012; 287, 12083-97.
DO Chemicals. OECD Guideline for testing of chemicals. The Organisation for Economic Co-operation and Development, Paris, France, 2005, p. 1-3.
N Beyhan, B Kocyigit-Kaymakcioglu, S Gümrü and F Aricioglu. Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones. Arabian. J. Chem. 2017; 10, S2073-S2081.
FA Oliveira, RND Almeida, MF Sousa, JM Barbosa-Filho, SA Diniz, IAD Medeiros. Anticonvulsant properties of N-salicyloyltryptamine in mice. Pharmacol. Biochem. Behav. 2001; 68, 199-202.
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