Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters

Yasmin H Momin; V C Yeligar; M G Saralaya; G Dharmamoorthy; B P Mallikarjuna; S T Jadhav; Kuntal Das; Mansour Almuqbil; Fuzail Ahmad; Syed Imam Rabbani; Syed Mohammed Basheeruddin Asdaq

doi:10.1016/j.compbiolchem.2024.108087

Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters

Comput Biol Chem. 2024 Jun:110:108087. doi: 10.1016/j.compbiolchem.2024.108087. Epub 2024 Apr 26.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, Annasaheb Dange College of B.Pharmacy, Ashta, MH 416301, India.
² Department of Pharmaceutical Chemistry, S Krishna Institute of Pharmacy, #39, Karad, Malkapur, Maharashtra 415539, India.
³ Department of Pharmaceutical Chemistry, MB School of Pharmaceutical Sciences, Mohan Babu University, Tirupati 517102, India.
⁴ Department of Pharmaceutical Chemistry, MB School of Pharmaceutical Sciences, Mohan Babu University, Tirupati 517102, India. Electronic address: mallibp@gmail.com.
⁵ Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra 517102, India.
⁶ Dept of Pharmacognosy, Mallige College of Pharmacy, #71, Silvepura, Chikkabanavara Post, Bengaluru 560090, India. Electronic address: drkkdsd@gmail.com.
⁷ Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: mmetwazi@ksu.edu.sa.
⁸ Department of Respiratory Therapy, College of Applied Sciences, AlMareefa University, Diriya, Riyadh, Saudi Arabia. Electronic address: fahmad@um.edu.sa.
⁹ Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
¹⁰ Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, Riyadh 13713, Saudi Arabia. Electronic address: sasdag@um.edu.sa.

PMID: 38718496
DOI: 10.1016/j.compbiolchem.2024.108087

Abstract

Introduction: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties.

Methods and materials: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET).

Results: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC₅₀ (median lethal dose) value of the isolated compound was found to be 64.36 μg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol^-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min^-1 kg^-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity.

Conclusion: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Keywords: 2; 4-di tertiary butyl phenol; ADMET; Alpha-amylase; Diabetes mellitus; Drug screening.

MeSH terms

Cucurbitaceae / chemistry
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology
Humans
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / isolation & purification
Hypoglycemic Agents / pharmacology
Molecular Docking Simulation*
Molecular Structure
Phenols* / chemistry
Phenols* / isolation & purification
Phenols* / pharmacology
alpha-Amylases* / antagonists & inhibitors
alpha-Amylases* / metabolism

Substances

alpha-Amylases
Phenols
Enzyme Inhibitors
Hypoglycemic Agents