Structural Characterization and Molecular Docking Screening of Most Potent 1,2,4-Triazine Sulfonamide Derivatives as Anti-Cancer Agents
Author:
Mutahir Sadaf12ORCID, Khan Muhammad Asim12ORCID, Naglah Ahmed M.3ORCID, Al-Omar Mohamed A.3ORCID, Almehizia Abdulrahman A.3ORCID, Huwaimel Bader4ORCID, Abouzied Amr S.45ORCID, Alharbi Amirah Senaitan6, Refat Moamen S.7ORCID
Affiliation:
1. School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, China 2. Department of Chemistry, University of Sialkot, Sialkot 51300, Pakistan 3. Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia 4. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, P.O. Box 2440, Hail 81442, Saudi Arabia 5. Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12553, Egypt 6. King Saud University Medical City, King Khalid University Hospital, P.O. Box 7805, Riyadh 11472, Saudi Arabia 7. Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Abstract
One of the biggest problems facing contemporary medicine is cancer. New approaches to therapy are required due to the difficult and prolonged treatment, the numerous adverse properties of the medications employed, and the developing confrontation of neoplastic cells to treatment. Ten 1,2,4-triazine sulfonamide derivatives (1–10) were chosen for the first time in the current work, and their chemical structures were examined by DFT studies. The in silico flexible docking analysis of the chosen receptors involved in cancer development and metastasis (3RHK, 5GTY, 6PL2, and 7JXH) revealed that the selected compounds are the most promising. The binding affinity of compounds 10, 2, 6, and 4 is much better than the standard drug, Erlotinib, whereas compounds 9, 3, 1, and 7 showed better affinities as compared to standard drugs Neratinib and Tepotinib in the case of 3RHK receptor. The binding affinity against the 5GTY receptor of compounds 10, 5, and 3 is much better than the standard drug Tepotinib, and compounds 7, 6, 2, 4, 1, 8, and 9 showed better than Erlonitib and Neratinib. The binding affinity against the 6PL2 receptor of compounds 8, 3, 5, 4, 9, and 1 is much better than the standard drug Tepotinib. Compounds 10, 6, 7, and 2 were better than Erlotinib and Neratinib. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor, whereas compounds 2, 10, 5, 9, and 8 are better than Erlotinib. In silico ADME experiments supported the identified compounds’ drug similarity. According to the MEP calculations, compounds 3 through 10 can interact non-covalently. The interactions might take the form of σ- and π-hole interactions. Softest compound 4 has the smallest energy gap, with an E-gap value of 3.25 Ev. Compound 4 has the largest energy gap at 3.41 eV. Compound 5 superior electron donor has the highest HOMO energy (6.5470 eV for HOMO). Compound 2 has the lowest LUMO energy, which suggests that it would be the best electron acceptor (ELUMO = 5.766364 eV).
Funder
Deanship of Scientific Research at King Saud University
Subject
Inorganic Chemistry,Condensed Matter Physics,General Materials Science,General Chemical Engineering
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