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Design, Synthesis, and Biological Evaluation of Benzo[cd]indol-2(1H)-ones Derivatives as a Lysosome-Targeted Anti-metastatic Agent.

ABSTRACT: Lysosomes have become a hot topic in tumor therapy; targeting the lysosome is therefore a promising strategy in cancer therapy. Based on our previous lysosome-targeted bio-imaging agent, homospermine-benzo[cd]indol-2(1H)-one conjugate (HBC), we further developed three novel series of polyamine- benzo[cd]indol-2(1H)-one conjugates. Among them, compound 15f showed potent inhibitory activity in hepatocellular carcinoma migration both in vitro and in vivo. Our study results showed that compound 15f entered the cancer cells via the polyamine transporter localized in the lysosomes and caused autophagy and apoptosis. The mechanism of action revealed that the crosstalk between autophagy and apoptosis induced by 15f was mutually reinforcing patterns. Besides, 15f also targeted lysosomes and exhibited stronger green fluorescence than HBC, which indicated its potential as an imaging agent. To summarize, compound 15f could be used as a valuable dual-functional lead compound for future development against liver-cancer metastasis and lysosome imaging.

SUBMITTER: Li J

PROVIDER: S-EPMC8446683 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Novel N-Substituted 2-(2-(Adamantan-1-yl)-1H-Indol-3-yl)-2-Oxoacetamide Derivatives: Synthesis and Biological Evaluation.

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N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation.

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Crystal structure of 5-(5-chloro-2-hydroxy-benzo-yl)-2-(2-methyl-1H-indol-3-yl)nicotino-nitrile.

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Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation.

Project description:Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The title compounds were prepared via PdCl₂-mediated endo-dig cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4a-k were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except 4h and 4i were found to be inactive against the three cancer cell lines. Compound 4h substituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone 4i, on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4a-l were found to be inactive against the chloroquine sensitive 3D7 strain of Plasmodium falciparum.

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Project description:The title compound, C24H20N2OS, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit, in each of which the cyclo-hexene rings adopt half-chair conformations. The mean plane of the indole ring is twisted from those of the phenyl and thio-phene rings by 69.0 (7) and 8.3 (5)°, respectively, in mol-ecule A and by 65.4 (9) and 6.7 (5)°, respectively, in mol-ecule B. The dihedral angles between the mean planes of the phenyl and thio-phene rings are 63.0 (4) and 58.8 (9)° in mol-ecules A and B, respectively. In the crystal, N-H⋯O hydrogen bonds lead to the formation of an infinite chain along [101]. In addition, π-π stacking inter-actions are observed involving the thio-phene and pyrrole rings of the two mol-ecules, with a shortest inter-centroid distance of 3.468 (2) Å.

| S-EPMC3998588 | biostudies-literature

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