Design, Synthesis and In Silico Evaluation of 1,3,4-Oxadiazole Derivatives for Their Nootropic Activity

Suvarna A Katti; Namrata  Revar; Sarvesh Sonawane; Shubhangi H Pawar; Rupali A Patil; Anuja P Bhosale; Manisha A Tayde

Suvarna A Katti Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Namrata Revar Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Sarvesh Sonawane Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Shubhangi H Pawar Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Rupali A Patil Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Anuja P Bhosale Department of Pharmaceutical Chemistry, MGV’S Pharmacy College, Panchavati, Nashik, Maharashtra, India.
Manisha A Tayde Department of Pharmaceutical Chemistry Panchavati Education Society’s Institute of Pharmacy, Panchavati, Nashik, India

Keywords: Nootropic, Alzheimer`s Disease, 1,3,4-oxadiazole

Abstract

Introduction: Computational methods have become indispensable in modern medicinal chemistry research, enabling the rapid screening and evaluation of potential drug candidates. This study leverages in silico approaches to investigate the neuroprotective potential of 1,3,4-oxadiazole derivatives. By employing software such as PASS online, SwissADME, ProTox-III, and Autodock Vina, we aimed to predict the biological activity, pharmacological properties, and toxicity profiles of these compounds.
Method: We utilised a combination of in silico techniques, including PASS online for predicting biological activity, SwissADME for assessing pharmacokinetic properties, ProTox-III for evaluating toxicity, and Autodock Vina for molecular docking studies. The predicted properties of the 1,3,4-oxadiazole derivatives were then compared with those of donepezil, a well-established neuroprotective drug. Furthermore, compounds exhibiting significant predicted activity were synthesised and subsequently characterised using analytical techniques such as TLC, FTIR, and NMR.
Results: The results from the PASS online analysis revealed that compound NR1 exhibited the highest predicted activity score (0.636) compared to donepezil (0.553). The predicted activity order was determined as NR1>NR7>NR2>NR3>NR5>NR6>NR4. Molecular docking studies further supported these findings, indicating that 2,5 diaryl 1,3,4-oxadiazole derivatives with polar group substitutions at specific positions (3, 4, and 5; 3, 5; or 2, 5) displayed favorable docking scores.
Conclusion: The in silico analyses conducted in this study suggest that 1,3,4-oxadiazole derivatives possess promising neuroprotective potential, comparable to the standard drug donepezil. These findings provide a valuable foundation for further experimental investigations and optimization of these compounds as potential therapeutic candidates for neurodegenerative disorders.

How to cite this article:
Katti S A, Revar N, Sonawane S, Pawar S H, Patil R A, Bhosale A P. Design, Synthesis and In Silico Evaluation of 1,3,4-Oxadiazole Derivatives for Their Nootropic Activity. Chettinad Health City Med J. 2024;13(4):43-54.

DOI: https://doi.org/10.24321/2278.2044.202458

References

Mao P, Reddy PH. Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer’s disease: implications for early intervention and therapeutics. Biochim Biophys Acta. 2011 Nov;1812(11):1359-70. [PubMed] [Google Scholar]

Chiroma SM, Taib CN, Moklas MA, Baharuldin MT, Amom Z, Jagadeesan S. The use of nootropics in Alzheimer’s disease: is there light at the end of the tunnel? Biomed Res Ther. 2019 Jan 4;6(1):2937-44. [Google Scholar]

Folch J, Petrov D, Ettcheto M, Abad S, Sánchez-López E, García ML, Olloquequi J, Beas-Zarate C, Auladell C, Camins A. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plast. 2016;2016:8501693. [PubMed] [Google Scholar]

De Andrade Ramos G, De Oliveira AS, Bartolini M, Naldi M, Liparulo I, Bergamini C, Uliassi E, Wu L, Fraser PE, Abreu M, Kiametis AS, Gargano R, Silveira ER, Brand GD, Prchal L, Soukup O, Korabecny J, Bolognesi ML, Romeiro LA. Discovery of sustainable drugs for Alzheimer’s disease: cardanol-derived cholinesterase inhibitors with antioxidant and anti-amyloid properties. RSC Med Chem. 2021;12(7):1154-63. [PubMed] [Google Scholar]

Begum F, Yousaf M, Iqbal S, Ullah N, Hussain A, Khan M, Khalid A, Algarni AS, Abdalla AN, Khan A, Lodhi MA, Al-Harrasi A. Inhibition of acetylcholinesterase with novel 1, 3, 4, oxadiazole derivatives: a kinetic, in silico, and in vitro approach. ACS Omega. 2023;8(49):46816-29. [PubMed] [Google Scholar]

Colucci L, Bosco M, Ziello AR, Rea R, Amenta F, Fasanaro AM. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review. J Exp Pharmacol. 2012 Dec;4:163. [PubMed] [Google Scholar]

Sengupta P, Mal M, Mandal S, Singh J, Maity TK. Evaluation of antibacterial and antifungal activity of some 1, 3, 4 oxadiazoles. Iran J Pharmacol Therap. 2008 Dec 1;7(2):165-7. [Google Scholar]

Bhardwaj N, Saraf SK, Sharma P, Kumar P. Syntheses, evaluation and characterization of some 1, 3, 4-oxadiazoles as antimicrobial agents. J Chem. 2009;6:698023. [Google Scholar]