Synthesis and biological evaluation of new bisindole-imidazopyridine hybrids as apoptosis inducers

Sunkari, Satish; Bonam, Srinivasa Reddy; Rao, A. V. Subba; Riyaz, Sd.; Nayak, Vijayashree; Kumar, Halmuthur M. Sampath; Kamal, Ähmed; Babu, Bathini Nagendra

doi:10.1016/j.bioorg.2019.03.061

Cited by 14 publications

(7 citation statements)

References 23 publications

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“…The relationship of the chemical structures (SARs) of the prepared compounds to the results mentioned in this study, in terms of the ability of these compounds to apply cytotoxicity activity to human carcinoma cells, is due to several possibilities, including the following: (A) The presence of the thienopyrimidinones, 1,2,4-triazolopyrimidinone, 1,4-thiazine, pyrrolo-1,2,4-triazole, pyrroloquinoxaline, oxathiinoquinoxaline, 1,4-oxathiinopyrrolotriazole, imidazopyrrolotriazole and 1,2,4-triazoloimidazopyrrolo-triazole moieties may be requested for a broad spectrum of the cytotoxicity activity. (B) 1,2,4triazoloimidazopyrrolotriazolothienopyrimidindione (20), imidazopyrrolotriazolo-thienopyrimidindione (19), thienopyrimidotriazolopyrrolooxathiinoquinoxalindione (17), thienopyrimidotriazolopyrroloquinoxalindione ( 16), 2-(((6-benzoyl-thienotriazolo-pyrimidin-2yl)methyl) thio)-thienotriazolopyrimidinene (11) and 1,4-oxathiinopyrrolo-triazolothienopyrimidin-trione ( 18) demonstrated great anticancer activity in vitro, and this corresponds to previous scientific studies, because numerous heterocyclic compounds have pharmacological activities, such as imidazoles, benzimidazoles, thieno-[2,3-d]pyrimidines, 1,2,4-triazoles, thiazolopyrimidines, pyrrolothiazolo-pyrimidines, pyrrolotriazines, pyrrolotriazepines, triazolopyrrolothiazolopyrimidines, quinolines, quinoxalines, thiazolidinones, thiazines, thienotriazoles, thiophenes, phenyl, benzoyl and methyl, which have displayed potent anticancer activity [2,5,8,10,20,25,34,38,40,[48][49][50]. (C) Thence, the compounds 20, 19, 17, 16, 11 and 18 offered high cytotoxicity against all human carcinoma cell lines, such as nasopharyngeal (CNE2), oral (KB), breast (MCF-7) and gastric (MGC-803), during the comparison with 5-Fluorouracil as a standard drug, shown in Table 2.…”

Section: Structural Activity Relationship (Sar)supporting

confidence: 74%

“…have pharmacological activities, such as imidazoles, benzimidazoles, thieno-[2,3-d]pyrimidines, 1,2,4-triazoles, thiazolopyrimidines, pyrrolothiazolo-pyrimidines, pyrrolotriazines, pyrrolotriazepines, triazolopyrrolothiazolopyrimidines, quinolines, quinoxalines, thiazolidinones, thiazines, thienotriazoles, thiophenes, phenyl, benzoyl and methyl, which have displayed potent anticancer activity[2,5,8,10,20,25,34,38,40,[48][49][50]. (C) Thence, the compounds 20, 19, 17, 16, 11 and 18 offered high cytotoxicity against all human carcinoma cell lines, such as nasopharyngeal (CNE2), oral (KB), breast (MCF-7) and gastric (MGC-803), during the comparison with 5-Fluorouracil as a standard drug, shown in Table2.…”

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confidence: 99%

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Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives

2021

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In this article, we showed the synthesis of new polycyclic aromatic compounds, such as thienotriazolopyrimidinones, N-(thienotriazolopyrimidine) acetamide, 2-mercapto-thienotriazolo-pyrimidinones, 2-(((thieno-triazolopyrimidine) methyl) thio) thieno-triazolopyrimidines, thieno-pyrimidotriazolo-thiazines, pyrrolo-triazolo-thienopyrimidines, thienopyrimido-triazolopyrrolo-quinoxalines, thienopyrimido-triazolo-pyrrolo-oxathiino-quinoxalinones, 1,4-oxathiino-pyrrolo- triazolothienopyrimidinones, imidazopyrrolotriazolothienopyrimidines and 1,2,4-triazoloimidazo- pyrrolotriazolothienopyrimidindiones, based on the starting material 2,3-diamino-6-benzoyl-5- methylthieno[2,3-d]pyrimidin-4(3H)-one (3). The chemical structures were confirmed using many spectroscopic ways (IR, 1H, 13C, −NMR and MS) and elemental analyses. A series of thiazine, imidazole, pyrrole, thienotriazolopyrimidine derivatives were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines, i.e., CNE2 (nasopharyngeal), KB (oral), MCF-7 (breast) and MGC-803 (gastric) carcinoma cells. The compounds 20, 19, 17, 16 and 11 showed significant cytotoxicity against types of human cancer cell lines.

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Section: Structural Activity Relationship (Sar)supporting

confidence: 74%

mentioning

confidence: 99%

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives

2021

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“…Two 2,6-disubstituted imidazo [4,5-b] pyridine compounds have high activity and selectivity against receptor tyrosine kinases AXL and MER in vitro [ 24 ]. Two new bisindole-imidazopyridine hybrids induce apoptosis in a human lung cancer cell line (A549) [ 25 ]. A new type of imidazopyridine compound selectively inhibits mTOR and exerts a strong antiproliferative effect against HeLa and NCM460 cell lines [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Wang

Song

et al. 2020

BioMed Research International

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Background. Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism. Methods. Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot. Results. Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis. Conclusion. Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

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“…HeLa cancer cell lines, and the SAR indicated that electron-donating group at C-5 position of indole moiety was generally more favorable than the electron-withdrawing group. [83] Among them, hybrids 41a,b (IC 50 : 1.65-7.9 μM) were more potent than the reference DIM (IC 50 : 4.9-10.8 μM) against the four cancer cell lines.…”

Section: Bisindole Hybridsmentioning

confidence: 95%

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Zhang

2020

Archiv der Pharmazie

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The bisindole moiety, as a versatile pharmacophore, is one of the widespread heterocycles in naturally occurring and synthetic bioactive compounds. The bisindole alkaloids derived from natural sources possess structural and mechanistic diversity, and they were found to be generally more active than monoindole alkaloids against various cancer cell lines. Moreover, some bisindole alkaloids such as the tubulin inhibitors, vinorelbine and vinblastine, have already been approved for cancer therapy, suggesting that bisindole alkaloids are a significant source of anticancer agents and lead hits. Bisindole hybrids have the potential to overcome drug resistance, enhance efficiency, and reduce severe side effects. The bisindole–lactam hybrid midostaurin has already been approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia who are FLT3 mutation‐positive, highlighting the importance of bisindole hybrids in the development of novel anticancer agents. In this review, we present a brief account of the bisindole alkaloids derived from nature and of synthetic hybrids with potential anticancer activity developed in the recent 10 years.

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Synthesis and biological evaluation of new bisindole-imidazopyridine hybrids as apoptosis inducers

Cited by 14 publications

References 23 publications

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

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