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IJPER · Lens · Design, Synthesis, Molecular Docking, in silico ADME Assessment of Pyrrole-Based Heterocyclic Amino Acid Derivatives as Potential Anticonvulsant Agent

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Article · Volume 58, Issue 3S · pp. s1062–s1074

Design, Synthesis, Molecular Docking, in silico ADME Assessment of Pyrrole-Based Heterocyclic Amino Acid Derivatives as Potential Anticonvulsant Agent

Md Shamsher Alam1, Mohammed Albratty1, Hassan Ahmed Alhazmi1,2,3, Asim Najmi1, Khalid Zoghebi1, Hafiz Antar Makeen4, Safaa Fathy Saleh1, Ahmed Farag El Kirdasy5, Benson Mathai Kochikuzhyil6

  1. 1Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, SAUDI ARABIA.
  2. 2Substance Abuse and Toxicology Research Centre, Jazan University, Jazan, SAUDI ARABIA.
  3. 3Medical Research Center, Jazan University, Jazan, SAUDI ARABIA.
  4. 4Department of Clinical Pharmacy, Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan, SAUDI ARABIA.
  5. 5Department of Biochemistry, College of Veterinary Medicine, Sadat City University, Sadat, EGYPT.
  6. 6Department of Pharmacology, Dr. Joseph Mar Thoma Institute of Pharmaceutical Sciences and Research, Kattanam, Alappuzha, Kerala, INDIA.

Abstract

Background Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsionsandoddbehaviour.Tenpyrrolecarbohydratebasedanalogues(Va-Vj)weresynthesized with amide as intermediate in the current research with the goal of reducing convulsions and seizures. Materials and Methods The newly developed compounds were synthesized. Numerous methods (IR, NMR, mass, elemental analysis, etc.,) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed ADME predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the GABA-A target protein. Results Anticonvulsant screening results identified compounds Ve, Vd, Vc and Va as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with Ile C:242, Asp C:424, Phe D:307, Arg C:250 Trp C:241 and Phe C:240 and the outcomes were good and in agreement with in vivo findings. Conclusion The study’s findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogues may therefore represent a possible lead and additional studies may result in a potential new drug candidate.

Keywords: N-glycosides; Carbohydrate; Anticonvulsant activity; Pyrrole; ADME

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