title: Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.
abstract: This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Somaia S
authors.initials: SS
authors.lastname: Abd El-Karim
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address: manal.hasan52@live.com.
authors.forename: Manal M
authors.initials: MM
authors.lastname: Anwar
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Neama A
authors.initials: NA
authors.lastname: Mohamed
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, 11795 Helwan, Cairo, Egypt.
authors.forename: Tamer
authors.initials: T
authors.lastname: Nasr
authors.affiliation: Green Chemistry Department, National Research Centre, Cairo, Egypt; School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Elseginy
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D011720:Pyrazoles
keywords: Anticancer; Benzofuran; Molecular docking; Pyrazole