1. Antiproliferative activity of NCI-DTP glutarimide derivatives. An alignment independent 3D QSAR study
- Author
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J Branko Drakulic, I Ljiljana Dosen-Micovic, O Ivan Juranic, and B Jelena Popovic-Djordjevic
- Subjects
alignment-independent 3D QSAR ,Quantitative structure–activity relationship ,010405 organic chemistry ,Stereochemistry ,Glutarimide ,General Chemistry ,01 natural sciences ,GRIND descriptors ,0104 chemical sciences ,lcsh:Chemistry ,antiproliferative agents ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:QD1-999 ,chemistry ,030220 oncology & carcinogenesis ,Antiproliferative Agents ,Molecular interaction fields ,Potency ,glutarimides - Abstract
Alignment-free, three dimensional structure-activity relationships (3D QSAR) of the antiproliferative potency of twenty-two glutarimide-containing compounds, taken from National Cancer Institute Developmental therapeutics Program database, toward eight representative human tumour cell lines are reported. The descriptors used in the QSAR study were derived from GRID molecular interaction fields. The obtained models readily detect structural motifs positively or negatively correlated with the potency of the studied compounds toward each cell line. In this way, the pharmacophoric pattern required for high potency of compounds is reported. This pattern can serve as guidance for the design and syntheses of novel congeners, planned to be tested toward human tumour cell lines. U tekstu je opisan odnos strukture i antiproliferativne aktivnosti 22 glutarimidna derivata prema osam reprezentativnih linija humanih tumora. Podaci o strukturi jedinjenja i njihovoj aktivnosti su preuzeti iz baze podataka Nacionalnog Instituta za rak, SAD. Deskriptori, nezavisni od poravnavanja molekula (GRIND-2), korišćeni u proučavanju odnosa strukture i aktivnosti su dobijeni upotrebom programa GRID. Modeli jasno prikazuju strukturne elemente jedinjenja koji se pozitivno ili negativno korelišu sa biološkom aktivnošću. Farmakoforna slika dobijena iz modela će biti korišćena za planiranje novih analoga koji sadrže glutarimidni prsten i za koje se očekuje da će pokazati značajnu antiproliferativnu aktivnost.
- Published
- 2010
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