title: Synthesis of some dihydropyrimidine-based compounds bearing pyrazoline moiety and evaluation of their antiproliferative activity.
abstract: Two series of 2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitriles 5a-h and 4-(4-chlorophenyl)-2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitriles 6a-h were synthesized via a cyclocondensation reaction of the corresponding 2-hydrazinopyrimidines 3a,b with the appropriate 2-propen-1-ones 4a-h. The target compounds were screened for their antiproliferative activity against A 549 (lung), HT 29 (colon), MCF 7 and MDA-MB 231 (breast) cell lines. The two most susceptible cell lines were the colon (HT 29) and breast (MDA-MB 231). Generally, the 4-unsubstitutedphenylpyrimidine derivatives 5a-h were more active than their 4-chlorophenylpyrimidine analogs 6a-h. Compounds 5e and 5g, showed high activity against three of the cell lines. The most active compound 5c possessed IC₅₀ = 1.76 μM against A 549 cell line.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Eini, 11562 Cairo, Egypt. Electronic address: fadi2mae@gmail.com.
authors.forename: Fadi M
authors.initials: FM
authors.lastname: Awadallah
authors.forename: Gary A
authors.initials: GA
authors.lastname: Piazza
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Gary
authors.forename: Adam B
authors.initials: AB
authors.lastname: Keeton
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Canzoneri
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines
keywords: Antiproliferative activity; Human breast (MDA-MB 231) cell line; Human colon (HT 29) cell line; Pyrazoline; Pyrimidine