title: Synthesis and anticancer activity of novel 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine derivatives.
abstract: A series of new 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines with different substituents as C-4 position was synthesized. The anticancer activity of the newly synthesized compounds was tested in vitro using a two-stage process utilizing 60 different human tumor cell lines representing leukemia, melanoma and cancers of lung, colon, central nervous system, ovary, kidney, prostate as well as breast. Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity at low concentrations against most of the used human tumor cell lines comparable with doxorubicin as standard potent anticancer drug (average log10 GI50 over all cell lines = -6.85). Also, compound 4b was selective against SNB-75 (CNS cancer) log10 GI50 = -5.57. Interestingly, compound 7e exhibited promising selectivity against 13 tumor cell lines showing growth inhibition percentages between 54.05 and 89.23.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Cairo University, 33 Kasr El-Aini Street, Cairo 11562, Egypt. asmaa_kassab2001@yahoo.com
authors.forename: Asmaa E
authors.initials: AE
authors.lastname: Kassab
authors.forename: Ehab M
authors.initials: EM
authors.lastname: Gedawy
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; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C584480:2-pyridyl hexahyrocyclooctathieno(2,3-d)pyrimidine; D000970:Antineoplastic Agents; D011725:Pyridines; D011743:Pyrimidines