title: Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities.
abstract: This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, SF-268, B16F-10) and cyclooxygenase (COX-2) protein expression inhibition in lipopolysaccharide (LPS)-activated rat monocytes. The results revealed that most of the synthesized compounds showed moderate-to-high cytotoxic activity against at least one cell line, with compound 10b being the most active against all used cell lines (IC50values 5.5-11 μg/ml) comparable to cisplatin. In addition, six of these compounds (7b, 10a-d, and 12c) demonstrated inhibition of LPS-induced COX-2 protein expression at low concentration (25 μg/ml) as compared to the control non-stimulated cells and showed a COX-2 selectivity index range comparable to diclofenac sodium. The overall results indicate that many of these pyrazolopyrimidine derivatives possess in vitro anti-inflammatory and anticancer activities at varying doses, and the most active compounds will be subjected to in vivo pharmacological evaluation.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Heba A
authors.initials: HA
authors.lastname: Abd El Razik
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American University, Byblos, Lebanon.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mroueh
authors.affiliation: School of Medicine, Lebanese American University, Byblos, Lebanon.
authors.forename: Wissam H
authors.initials: WH
authors.lastname: Faour
authors.affiliation: Department of Natural Sciences, School of arts and sciences, Lebanese American University, Byblos, Lebanon.
authors.forename: Wassim N
authors.initials: WN
authors.lastname: Shebaby
authors.affiliation: Department of Natural Sciences, School of arts and sciences, Lebanese American University, Byblos, Lebanon.
authors.forename: Costantine F
authors.initials: CF
authors.lastname: Daher
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Hayam M A
authors.initials: HMA
authors.lastname: Ashour
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Hanan M
authors.identifier: 0000-0001-5716-9307
authors.initials: HM
authors.lastname: Ragab
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D061986:MCF-7 Cells; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
chemical_list: C000622441:2-(4-(2-chlorophenyl)piperazin-1-yl)- N'-(1-phenyl-1H-pyrazolo(3,4-d)pyrimidin-4-yl)acetohydrazide; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011743:Pyrimidines; D004008:Diclofenac; C014175:pyrazolo(3,4-d)pyrimidine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: COX-2; antineoplastic agents; inflammation; purine bioisosteres