title: Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents.
abstract: In trying to develop new anticancer agents, a series of 1H-pyrazolo[3,4-b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivatives was investigated as a potential mechanism for the anticancer activity using DNA/methyl green assay and association constants assay. Compounds 19, 20, 21, 24 and 25 exhibited good activity against the four cancer cells comparable to that of doxorubicin. Interestingly, DNA binding assay results were in agreement with that of the cytotoxicity assays where the most potent anticancer compounds showed good DNA binding affinity comparable to that of doxorubicin and daunorubicin. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, DNA (PDB-code: 152d).
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. Electronic address: Ibrahimeissa@azhar.edu.eg.
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Eissa
authors.affiliation: Chemistry Department, Faculty of Science, Ain Shams University, Abbassiya, Cairo 11566, Egypt.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: El-Naggar
authors.affiliation: Chemistry Department, Faculty of Science, Ain Shams University, Abbassiya, Cairo 11566, Egypt.
authors.forename: Maher A
authors.initials: MA
authors.lastname: El-Hashash
mesh_terms: D000970:Antineoplastic Agents / 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; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C478081:1H-pyrazolo(3,4-b)pyridine; D000970:Antineoplastic Agents; D011720:Pyrazoles; D011725:Pyridines
keywords: 1H-pyrazolo[3,4-b]pyridine; Anticancer; DNA binding; Docking