Design, Synthesis and Molecular Docking Studies of Novel Cyclic Pentapeptides Based on Phthaloyl Chloride with Expected Anticancer Activity

Mohamed, Fatma Hassan; Shalaby, Ahmed; Soliman, Hanan Abdelhameid; Abdelazem, Ahmed; Mounier, Marwa; Nossier, Eman; Moustafa, Gaber

doi:10.21608/ejchem.2019.18452.2137

Design, Synthesis and Molecular Docking Studies of Novel Cyclic Pentapeptides Based on Phthaloyl Chloride with Expected Anticancer Activity

Document Type : Original Article

Authors

¹ Peptide Chemistry Department, National Research Centre, Dokki 12622, Cairo, Egypt

² Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Cairo, Egypt

³ Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

⁴ Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Egypt

⁵ Pharmaceutical and Drug Industries Research Division, Department of Pharmacognosy, National Research Centre, Giza, Egypt

⁶ Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

10.21608/ejchem.2019.18452.2137

Abstract

A series of Nα-phthaloyl bridged cyclic pentapeptide derivatives were synthesized and characterized on the basis of spectral and elemental analyses. A preliminary cytotoxicity evaluation of all novel compounds was carried out against four human cancer cell lines, human lung (A-549), colon (CaCo-2), prostate (PC-3) and breast (MCF-7) cancer cells at 100 μM concentration using MTT growth inhibition assay. Compound 3 gave the highest cytotoxic activity towards the human colon (CaCo-2) cancer cell line (Growth Inhibition = 72.4 %). Further molecular docking of the promising derivative 3 was developed to study its binding mode within the active site of EGFR enzyme. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues to elicit anticancer activity

Keywords