Synthesis and antiproliferative evaluation of 5-oxo and 5-thio derivatives of 1,4-diaryl tetrazoles.
A series of 1,4-diaryl tetrazol-5-ones were synthesized by copper mediated N-arylation of 1-phenyl-1H-tetrazol-5(4H)-one with aryl boronic acids, o-R(1)C(6)H(4)B(OH)(2) where R(1)=H, OMe, Cl, CF(3), Br, CCH. The 1,4-diaryl tetrazol-5-ones substituted with OMe, Cl, CF(3), Br underwent thionation with Lawesson's reagent to yield the corresponding 5-thio derivatives. The 1-(2-bromophenyl)-4-phenyl-1H-tetrazole-5(4H)-thione so obtained was subjected to lithiation/protonation and Sonogashira coupling to produce 1,4-diphenyl-1H-tetrazole-5(4H)-thione and 1-(2-ethynylphenyl)-4-phenyl tetrazole-5-thione, respectively. The title compounds were found to be stable to strong Lewis acid conditions. Three of these novel compounds were found to inhibit L1210 leukemia cell proliferation and SK-BR-3 breast cancer cell growth over several days in culture in vitro. Shorter tetrazole derivative treatments also reduced the expression of the Ki-67 marker of cell proliferation in SK-BR-3 cells and the rate of DNA synthesis in L1210 cells.
Gundugola
Aditya S
AS
Department of Chemistry, Kansas State University, Manhattan, 66506-0401, USA.
Chandra
Kusum Lata
KL
Perchellet
Elisabeth M
EM
Waters
Andrew M
AM
Perchellet
Jean-Pierre H
JP
Rayat
Sundeep
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D013777:Tetrazoles