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

Gursoy A., Karali N. L.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.38, ss.633-643, 2003 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1016/s0223-5234(03)00085-0
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.633-643
  • Anahtar Kelimeler: 1H-indole-2,3-diones, 3-phenyl-4(3H)-quinazolinones, hydrazones, cytotoxicity, NATIONAL-CANCER-INSTITUTE, IMPACT MASS-SPECTRA, REVERSE-TRANSCRIPTASE, DRUG DISCOVERY, CELL-LINES, DERIVATIVES, INHIBITORS, HIV-1, SPECTROMETRY, TUBULIN
  • İstanbul Üniversitesi Adresli: Evet

Özet

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(3H)-quinazolinone-2-yl)mercaptoacetic acid hydrazides (3a-e) with 1H- indole-2,3-diones (4a-e) furnished the corresponding 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones (5a-u). The structures of new compounds were determined by analytical and spectral (IR, H-1-NMR, C-13-NMR, EIMS) methods. Previously reported 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-bromo-1H-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(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-fluoro-1H-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. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.