Pharmacophoric features of the binding models Hypo 4/15 and Hypo9/12 (HBD as violet vectored spheres and Hbic as blue spheres, PosIon as red spheres, RingArom as orange vectored spheres, and ...exclusion volumes as gray spheres), fitted against the most active hit 120 (IC50=1.43 μM, Table 4).
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•Pharmacophoric space of 115 (HER2/ErbB2) inhibitors was explored.•Two pharmacophore models, Hypo4/15 and Hypo9/12, illustrated the best performance.•In silico screening of NCI and DrugBank databases identified 80 potential HER2 inhibitors.•4 of investigated hits selectively inhibited the growth of SKOV3 ovarian cells with IC50<5μM.
To discover potential antitumor agents directed toward human epidermal growth factor receptor-2HER2/ErbB2 overexpression in cancer, we have explored the pharmacophoric space of 115 HER2/ErbB2 inhibitors. This identified 240 pharmacophores which were subsequently clustered into 20 groups and cluster centers were used as 3D-pharmacophoric descriptors in QSAR analysis with 2D-physicochemical descriptors to select the optimal combination. We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Two binding pharmacophore models emerged in the optimal QSAR equation, suggesting the existence of distinct binding modes accessible to ligands within the HER2/ErbB2 binding pocket. The QSAR equation and its associated pharmacophore models were employed to screen the National Cancer Institute (NCI) and Drug Bank databases to search for new, promising, and structurally diverse HER2 inhibitory leads. Inhibitory activities were tested against HER2-overexpressing SKOV3 Ovarian cancer cell line and MCF-7 which express low levels of HER2. In silico mining identified 80 inhibitors out of which four HER2 selective compounds inhibited the growth of SKOV3 cells with IC50 values < 5μM and with virtually no effect in MCF-7 cells. These lead compounds are excellent candidates for further optimization.
Aqueous extracts of nine plants, known to have medicinal activity, were tested for their toxicity against the sweet potato whitefly, Bemisia tabaci Genn. (Homoptera: Aleurodidae) compared to the ...toxicity of the insecticide, Imidacloprid. Extracts of Lepidiuim sativum L. (Brassicales: Brassicaceae) killed 71 % of early stage nymphs, which was not significantly different from mortality caused by Imidacloprid. Treatment of pupae with three plant extracts, L. sativum, Achillea biebersteinii L. (Asterales: Asteraceae), or Retama raetam (Forssk.) Webb and Berthel (Fabales: Fabaceae) prevented adult development, and treatment with R. raetam extract killed adults, at levels that were not significantly different from Imidacloprid. None of the other plants showed significant toxicity. However extracts of four plants, Pimpinella anisum L. (Apiales: Apiaceae), Galium longifolium (Sibth. and SM.) (Gentianales: Rubiaceae), R. raetam and Ballota undulata Bentham (Lamiales: Lamiaceae) had a repellent effect.
Aqueous extracts of nine plants, known to have medicinal activity, were tested for their toxicity against the sweet potato whitefly, Bemisia tabaci Genn. (Homoptera: Aleurodidae) compared to the ...toxicity of the insecticide, Imidacloprid. Extracts of Lepidiuim sativum L. (Brassicales: Brassicaceae) killed 71 % of early stage nymphs, which was not significantly different from mortality caused by Imidacloprid. Treatment of pupae with three plant extracts, L. sativum, Achillea biebersteinii L. (Asterales: Asteraceae), or Retama raetam (Forssk.) Webb and Berthel (Fabales: Fabaceae) prevented adult development, and treatment with R. raetam extract killed adults, at levels that were not significantly different from Imidacloprid. None of the other plants showed significant toxicity. However extracts of four plants, Pimpinella anisum L. (Apiales: Apiaceae), Galium longifolium (Sibth. and SM.) (Gentianales: Rubiaceae), R. raetam and Ballota undulata Bentham (Lamiales: Lamiaceae) had a repellent effect.
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