Hamid Moghimi Benhangi1, Sheida Ahmadi2, Mohammad Hakimi2, Azam Molafilabi3, Habibollah Faraji4, Baratali Mashkani5. 1. Department of Medical Toxicology, Islamic Azad University, Shahreza, Iran. 2. Department of Chemistry, Payame Noor University, Tehran 19395-4697, Iran. 3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. 4. Department of Laboratory Sciences, Faculty of Para-Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. 5. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: mashkaniba@mums.ac.ir.
Abstract
INTRODUCTION: While some metals are required for physiological functions in the form of essential trace elements, they can cause toxicity in the excessive concentrations. Chelation therapy was used to reduce the adverse effects of acute and chronic poisoning by metals. Isatin derivatives form complexes with copper ions indicating that they may have protective activity against metal overload. METHOD: In this study, four compounds (isatin and three isatin-derivatives Mj1, TR and Mk1) were evaluated for drug-likeliness. Then their potency inhibiting cell proliferation was determined in HEK293 cell culture assay. Finally, IC50 values for lead, copper, and iron was evaluated in the absence and also the presence of isatin and its derivatives. RESULTS: Isatin and its derivatives used in this study complied with the Lipinski criteria for drug-likeliness. The greatest difference between the IC50 values and the non-toxic dose was obtained for TR and Mj1, respectively. Pretreatment with the Mj1 increased the IC50 values for lead, iron, and copper, by 2.1, 1.7 and 1.7 times, respectively. At non-toxic dose, TR has only increased the IC50 values for lead and copper by 1.4 and 1.3 times without affecting iron cytotoxicity. Mk1 increased the IC50 values for lead, copper, and iron by 1.3, 1.8 and 1.7 times, respectively. CONCLUSIONS: Mj1 is suggested as a lead compound for developing therapeutic agents for lead (Pb) toxicity and Mk1 for copper and iron.
INTRODUCTION: While some metals are required for physiological functions in the form of essential trace elements, they can cause toxicity in the excessive concentrations. Chelation therapy was used to reduce the adverse effects of acute and chronic poisoning by metals. Isatin derivatives form complexes with copper ions indicating that they may have protective activity against metal overload. METHOD: In this study, four compounds (isatin and three isatin-derivatives Mj1, TR and Mk1) were evaluated for drug-likeliness. Then their potency inhibiting cell proliferation was determined in HEK293 cell culture assay. Finally, IC50 values for lead, copper, and iron was evaluated in the absence and also the presence of isatin and its derivatives. RESULTS:Isatin and its derivatives used in this study complied with the Lipinski criteria for drug-likeliness. The greatest difference between the IC50 values and the non-toxic dose was obtained for TR and Mj1, respectively. Pretreatment with the Mj1 increased the IC50 values for lead, iron, and copper, by 2.1, 1.7 and 1.7 times, respectively. At non-toxic dose, TR has only increased the IC50 values for lead and copper by 1.4 and 1.3 times without affecting ironcytotoxicity. Mk1 increased the IC50 values for lead, copper, and iron by 1.3, 1.8 and 1.7 times, respectively. CONCLUSIONS: Mj1 is suggested as a lead compound for developing therapeutic agents for lead (Pb) toxicity and Mk1 for copper and iron.
Authors: Saeed Ali Syed; Ahmed Bari; Mohammed S Aldughaim; Md Abdur Rashid; Mohammad Hossain Shariare; Mohsin Kazi Journal: Molecules Date: 2020-12-22 Impact factor: 4.411
Authors: Ismail Luhar; Salmabanu Luhar; Mohd Mustafa Al Bakri Abdullah; Rafiza Abdul Razak; Petrica Vizureanu; Andrei Victor Sandu; Petre-Daniel Matasaru Journal: Materials (Basel) Date: 2021-12-04 Impact factor: 3.623