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- W4200016784 abstract "A series of heterocyclic compounds containing spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Antiproliferative activity of synthesized products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Spiroadducts with all cis bridge-protons of pyrrolo[3,4-a]pyrrolizine moiety were more active in all cases. Replacement of hydrogen atom of pyrrole moiety by either alkyl or aryl group leads to significant decreasement in activity of both formed cycloadducts. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induce apoptosis. Using confocal microscopy, we found that with synthesized products treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76-91% of cells. We discovered that HeLa cells after treatment with screened compounds significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and decrease in cell motility. All obtained data make it possible to assume that spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework may be considered as a new promising pharmacophore unit for further screenings." @default.
- W4200016784 created "2021-12-31" @default.
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- W4200016784 date "2021-11-02" @default.
- W4200016784 modified "2023-09-24" @default.
- W4200016784 title "Identification of spiro-fused pyrrolo[3,4-a]pyrrolizines and tryptanthrines as potential antitumor agents: Synthesis and initial <em>in vitro</em> evaluation" @default.
- W4200016784 doi "https://doi.org/10.3390/ecmc2021-11432" @default.
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