Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones

Abstract

New esters ( 2b and 2c) and hydrazides ( 3b and 3c) were synthesized from 6-methyl/fluoro-3-phenyl-4(1H, 3H)-quinazolinone-2-thiones ( 1b and 1c). Subsequent treatment of 3-phenyl-4(3 H)-quinazolinone-2-yl)mercaptoacetic acid hydrazides ( 3a– e) with 1 H-indole-2,3-diones ( 4a– e) furnished the corresponding 3-[[(3-phenyl-4(3 H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1 H-2-indolinones ( 5a– u). The structures of new compounds were determined by analytical and spectral (IR, 1H-NMR, 13C-NMR, EIMS) methods. Previously reported 3-[[(3-phenyl-4(3 H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-bromo-1 H-2-indolinone 5v and compounds 5b, 5d and 5o chosen as prototypes were evaluated against the full panel of 60 human tumour cell lines at a minimum of five concentrations at tenfold dilutions in the National Cancer Institute in vitro primary cytotoxicity assay. Sulforhodamine B protein assay was used to estimate cell stability or growth. 3-[[(6-Chloro-3-phenyl-4(3 H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-fluoro-1 H-2-indolinone 5o showed the most favourable cytotoxicity against a renal cancer cell line UO-31 (log 10 GI 50 value −6.68). Compound 5v was also tested against human immunodeficiency virus 1 (HIV-1). Compound 5v was confirmed moderately active against HIV-1.