A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes
Javed Ahmed,
Mohsin Abbas Khan,
Muhammad Ehsan Khalid,
Irshad Ahmad,
Irfan Pervaiz,
Umair Khurshid,
Saharish Khaliq,
Kashif ur Rehman Khan,
Muhammad Adeel Arshad,
Ghadeer M. Albadrani,
Ahmed E. Altyar,
Amany A. Sayed,
Mousa O. Germoush,
Mohamed M. Abdel-Daim
Affiliations
Javed Ahmed
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Mohsin Abbas Khan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Muhammad Ehsan Khalid
Frontier Medical and Dental College, Abbottabad 22020, Pakistan
Irshad Ahmad
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Irfan Pervaiz
KITAAS, Khaldunia College of Pharmacy, Lahore 54000, Pakistan
Umair Khurshid
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Saharish Khaliq
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Kashif ur Rehman Khan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Muhammad Adeel Arshad
Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore 54000, Pakistan
Ghadeer M. Albadrani
Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Ahmed E. Altyar
Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
Amany A. Sayed
Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt
Mousa O. Germoush
Biology Department, College of Science, Jouf University, P.O. Box 2014, Sakaka 72388, Saudi Arabia
Mohamed M. Abdel-Daim
Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia
The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1–MCu9) and Zn II (MZn1–MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives’ biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski’s rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.
