Synthesis and anticancer activity of oxindole derived imidazo[1,5-a]pyrazines

Kamal, Ähmed; Ramakrishna, G.; Raju, P. V. K.; Rao, A. V. Subba; Arutla, Viswanath; Nayak, V. Lakshma; Sistla, Ramakrishna

doi:10.1016/j.ejmech.2011.03.027

Cited by 79 publications

(37 citation statements)

References 26 publications

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“…The microtubules continuously undergo polymerization and depolymerization and inhibition of tubulin polymerization disturbs the assembly of microtubules; we analyzed the levels of soluble versus polymerized forms of tubulin in DU-145 cells. 38 It was considered of interest to investigate the apoptosis inducing effect of these conjugates by the Hoechst staining (H 33258) method in the DU-145 cancer cell line. 37 Based on results, we observed that more tubulin content present in the supernatant fraction than pellet fraction, while the tubulin in the supernatant fraction showed an increased level of free tubulin at 3 µM of 6q, 6r, 6s and E7010 whereas in the pellet it showed decrease of polymerized tubulin.…”

Section: Biologymentioning

confidence: 99%

Synthesis of 2-anilinopyridyl–triazole conjugates as antimitotic agents

et al. 2015

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A series of 2-anilinopyridyl–triazole conjugates (6a–t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 μM. Structure–activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.

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Section: Biologymentioning

confidence: 99%

Synthesis of 2-anilinopyridyl–triazole conjugates as antimitotic agents

et al. 2015

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“…1) having benzimidazole moiety as its basic scaffold is a well known agent that inhibits tubulin polymerization. On the other hand oxindoles are versatile molecules that display diverse biological activities, including anticancer activity [26,27]. For example, Indirubin (4, Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of benzimidazole–oxindole conjugates as microtubule-targeting agents

Kamal

Nagaseshadri

Nayak

et al. 2015

Bioorganic Chemistry

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“…The imidazo [1,5-a]pyridines are an important class of 10π-electron fused nitrogencontaining heterocyclic compounds due to their biological activity [15][16][17][18] and special photophysical properties. The later have turned them, for example, potential materials for organic light-emitting diodes (OLED) [19] and organic field-effect transistors (OFET) [20].…”

Section: Introductionmentioning

confidence: 99%