Molecular docking, drug-likeness and DFT study of some modified tetrahydrocurcumins as potential anticancer agents

Ahmed Mahal; Marwan Al-Janabi; Volkan Eyüpoğlu; Anas Alkhouri; Samir Chtita; Mustafa M Kadhim; Ahmad J Obaidullah; Jawaher M Alotaibi; Xiaoyi Wei; Mohammad Rizki Fadhil Pratama

doi:10.1016/j.jsps.2023.101889

Molecular docking, drug-likeness and DFT study of some modified tetrahydrocurcumins as potential anticancer agents

Saudi Pharm J. 2024 Jan;32(1):101889. doi: 10.1016/j.jsps.2023.101889. Epub 2023 Dec 1.

Authors

Affiliations

¹ Department of Medical Biochemical Analysis, College of Health Technology, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq.
² Department of Chemistry, Çankırı Karatekin University, Çankırı, Turkey.
³ College of Pharmacy, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq.
⁴ Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
⁵ Department of Dentistry, Kut University College, Kut, Wasit 52001, Iraq.
⁶ Medical Laboratory Techniques Department, Al-Farahidi University, Baghdad, 10022, Iraq.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
⁸ Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement and Guangdong Provincial Key Laboratory of Digital Botanical Garden and Public Science, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, People's Republic of China.
⁹ University of Chinese Academy of Sciences, Yuquanlu 19A, Beijing 100049, People's Republic of China.
¹⁰ Department of Pharmacy, Universitas Muhammadiyah Palangkaraya, Palangka Raya, Central Kalimantan 73111, Indonesia.

Abstract

The present study utilized molecular docking and density functional theory (DFT) approaches, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties to investigate the binding interactions, reactivity, stability, and drug-likeness of curcumin (1), tetrahydrocurcumin (2), and tetrahydrocurcumin derivatives (3-6) as potential anti-cancer agents. MGL (Molecular Graphic Laboratory) and Discovery Studio Visualizer (DSV) software employed for docking studies. Pharmacokinetic and pharmacodynamic (ADME-Tox) analyses were conducted using SwissADME and pKCSM web servers. Total Electron Density (TED) measurements identified molecular adsorption sites, considering various factors, including quantum chemical characteristics, to assess compound effectiveness using DFT method implanted in the Gaussian software. The binding energy (Eb) from docking simulations was used to evaluate inhibitory potential. ADMET analysis suggested favorable oral bioavailability and pharmacokinetics for all studied substances, excluding compound 4. DFT and docking investigations highlighted compounds 1, 2, and 6 as optimal scaffolds for drug design based on in silico screening tests.

Keywords: ADMET; Anticancer; DFT; Docking; Tetrahydrocurcumin.