Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4] benzothiadiazine linked pyrrolo[2,1-c] [1,4] benzodiazepine conjugates

被引:42
作者
Kamal, Ahmed [1 ]
Khan, M. Naseer A. [1 ]
Srikanth, Y. V. V. [1 ]
Reddy, K. Srinivasa [1 ]
Juvekar, Aarti [2 ]
Sen, Subrata [2 ]
Kurian, Nisha [2 ]
Zingde, Surekha [2 ]
机构
[1] Indian Inst Chem Technol, Div Organ Chem, Biol Chem Lab, Hyderabad 500007, Andhra Pradesh, India
[2] Adv Ctr Treatment Res & Educ Canc, Navi Mumbai 410210, India
关键词
triazolobenzothiadiazines; pyrrolobenzodiazepine; antitumour activity; DNA-binding ability;
D O I
10.1016/j.bmc.2008.06.056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of triazolobenzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These compounds have exhibited significant cytotoxicity against most of the cell lines examined. Compound 5a displays GI(50) values from 1.83 to 2.38 mu M against seven human tumour cell lines, and is identified as a promising lead compound from this series. Their DNA thermal denaturation studies have also been carried out, and one of the compounds 5c elevates the DNA helix melting temperature of the CT-DNA by 2.6 degrees C after incubation for 36 h. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7804 / 7810
页数:7
相关论文
共 42 条
  • [1] ADAMSON RH, 1972, NATURE, V236, P400, DOI 10.1038/236400a0
  • [2] DEXTROCHRYSIN A NEW ANTIBIOTIC
    AOKI, H
    MIYAIRI, N
    AJISAKA, M
    SAKAI, H
    [J]. JOURNAL OF ANTIBIOTICS, 1969, 22 (05) : 201 - &
  • [3] BRIEN ME, 1992, CANCER CHEMOTH PHARM, V30, P245
  • [4] Buzdar AU, 2002, BREAST CANCER RES TR, V75, pS13
  • [5] Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8′ ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers
    Gregson, SJ
    Howard, PW
    Gullick, DR
    Hamaguchi, A
    Corcoran, KE
    Brooks, NA
    Hartley, JA
    Jenkins, TC
    Patel, S
    Guille, MJ
    Thurston, DE
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (05) : 1161 - 1174
  • [6] HAINSWORTH JD, 1989, CANCER RES, V49, P5217
  • [7] Holla BS, 2002, EUR J MED CHEM, V37, P511
  • [8] HOUGHTON PJ, 1990, CANCER RES, V50, P664
  • [9] STUDIES ON THE CELLULAR PHARMACOLOGY OF N-(4-METHYLPHENYLSULFONYL)-N'-(4-CHLOROPHENYL)-UREA
    HOUGHTON, PJ
    BAILEY, FC
    GERMAIN, GS
    GRINDEY, GB
    HOWBERT, JJ
    HOUGHTON, JA
    [J]. BIOCHEMICAL PHARMACOLOGY, 1990, 39 (07) : 1187 - 1192
  • [10] HOUGHTON PJ, 1990, CANCER RES, V50, P318