Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study
El-Masry, R., Amin, M., Korani, M., Giovannuzzi, S., sakr, T., Kadry, H., Supuran, C., Shaarawy, S., Shalaby, A. (2023). Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study. EKB Journal Management System, 66(7), 19-30. doi: 10.21608/ejchem.2022.162655.6977
Rana Magdy El-Masry; Mohamed A Amin; Mohamed Korani; Simone Giovannuzzi; tamer mostafa sakr; Hanan Hassan Kadry; Claudiu T Supuran; Sahar Shaarawy; Azza Taher Shalaby. "Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study". EKB Journal Management System, 66, 7, 2023, 19-30. doi: 10.21608/ejchem.2022.162655.6977
El-Masry, R., Amin, M., Korani, M., Giovannuzzi, S., sakr, T., Kadry, H., Supuran, C., Shaarawy, S., Shalaby, A. (2023). 'Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study', EKB Journal Management System, 66(7), pp. 19-30. doi: 10.21608/ejchem.2022.162655.6977
El-Masry, R., Amin, M., Korani, M., Giovannuzzi, S., sakr, T., Kadry, H., Supuran, C., Shaarawy, S., Shalaby, A. Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study. EKB Journal Management System, 2023; 66(7): 19-30. doi: 10.21608/ejchem.2022.162655.6977

Elaborating 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Scaffold with A P-Tolyl Sulfonamide Moiety Enhances Cytotoxic Activity: Design, Synthesis, in Vitro Cytotoxicity Evaluation, Radiolabelling and in Vivo Pharmacokinetic Study

Egyptian Journal of Chemistry
Volume 66, Issue 7, July 2023, Page 19-30  XML PDF (425.86 K)
Document Type: Original Article
DOI: 10.21608/ejchem.2022.162655.6977
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Authors
Rana Magdy El-Masry email orcid 1; Mohamed A Amin2; Mohamed Korani3; Simone Giovannuzzi4; tamer mostafa sakr5; Hanan Hassan Kadry6; Claudiu T Supuran7; Sahar Shaarawy8; Azza Taher Shalaby9
1Elwahat Street, 6 october city, Egypt
2Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt.
3Radioisotopes Production Facility (RPF), Egyptian Second Research Reactor (ETRR‑2), Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt
4Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy
5Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo 13759, Egypt.
6Department of pharmaceutical organic chemistry, Faculty of pharmacy, Cairo University, Cairo, Egypt
7Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy
8Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
9Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
Abstract
Novel 1,3,4-thiadiazole derivatives (3-5) were designed, synthesized, and screened for cytotoxic activity. Compound 3 bearing substituted benzenesulfonamide scaffold exhibited remarkable potency against breast cancer (MCF-7), hepatoma (HepG2), colon cancer (HCT116), and lung cancer (A549) cells and lower potency on the normal cells (WI-38), as well as, it possesses higher anticancer activity than starting 5-(4-chlorophenyl)-1,3,4-thiadiazole-2-amine (2) and the positive control Staurosporine. The anticancer activity of compound 3 is at least partly attributed to the inhibition of the tumor-associated human carbonic anhydrase isoforms IX and XII. The high selectivity of compound 3 for cancer cells over normal cells and for tumor-associated CA isoforms IX and XII over the off-target cytosolic isoform II reflects its safety. Pharmacokinetic study of compound 3 was evaluated in a normal mice model based on a radiopharmaceutical chemistry approach.
Keywords
1; 3; 4-thiadiazoles; sulfonamides; carbonic anhydrase inhibitors; anticancer activity; radioactive tracing study
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