Synthesis and in vitro anticancer activity evaluation of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-c]pyrazole] via sequential four-component reaction
TL;DR: In this article, a rapid and simple strategy for synthesis of spiro[indolo[2,1-b]quinazoline-pyrano [2,3-c]pyrazole derivatives via sequential four-component reaction of isatoic anhydride, isatin, malononitrile, and 3-methyl-pyrazolones in CH2Cl2 at room temperature is described.
About: This article is published in Journal of Molecular Structure.The article was published on 2022-02-15. It has received 2 citations till now. The article focuses on the topics: Chemistry & Isatin.
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TL;DR: In this paper , a thermal one-pot multi-component strategy was used to synthesize 24 tryptanthrin-thiopyrano[2,3-b]indole hybrid molecules.
4 citations
TL;DR: The results support this idea that the compounds 4a and 4e may be potential for drug designing in cancer therapy, however, more experiments will be required to find possible side effects of related compounds in vivo.
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TL;DR: The discovery of HA14-1, a small molecule and nonpeptidic ligand of a Bcl-2 surface pocket, provides a chemical probe to study B cl-2-regulated apoptotic pathways in vivo and could lead to the development of new therapeutic agents.
Abstract: Bcl-2 and related proteins are key regulators of apoptosis or programmed cell death implicated in human disease including cancer. We recently showed that cell-permeable Bcl-2 binding peptides could induce apoptosis of human myeloid leukemia in vitro and suppress its growth in severe combined immunodeficient mice. Here we report the discovery of HA14-1, a small molecule (molecular weight = 409) and nonpeptidic ligand of a Bcl-2 surface pocket, by using a computer screening strategy based on the predicted structure of Bcl-2 protein. In vitro binding studies demonstrated the interaction of HA14-1 with this Bcl-2 surface pocket that is essential for Bcl-2 biological function. HA14-1 effectively induced apoptosis of human acute myeloid leukemia (HL-60) cells overexpressing Bcl-2 protein that was associated with the decrease in mitochondrial membrane potential and activation of caspase-9 followed by caspase-3. Cytokine response modifier A, a potent inhibitor of Fas-mediated apoptosis, did not block apoptosis induced by HA14-1. Whereas HA14-1 strongly induced the death of NIH 3T3 (Apaf-1+/+) cells, it had little apoptotic effect on Apaf-1-deficient (Apaf-1−/−) mouse embryonic fibroblast cells. These data are consistent with a mechanism by which HA14-1 induces the activation of Apaf-1 and caspases, possibly by binding to Bcl-2 protein and inhibiting its function. The discovery of this cell-permeable molecule provides a chemical probe to study Bcl-2-regulated apoptotic pathways in vivo and could lead to the development of new therapeutic agents.
1,158 citations
TL;DR: An ecofriendly green approach for synthesis of substituted pyrano[2,3-c]pyrazoles has been developed via a multicomponent one pot approach in aqueous ethanol medium under totally non-catalytic conditions.
144 citations
TL;DR: A natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures and led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level.
Abstract: Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure–activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3+ regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.
143 citations
TL;DR: 8-desbromohinckdentine A is synthesized from a 2-aryl indole by first preparing the quaternary center of the natural product and then building the seven-membered lactam and dihydropyrimidine rings onto this intermediate to form the framework of hinckerdentines A.
Abstract: Hinckdentine A is an alkaloid isolated from the bryozoan Hincksinoflustra denticulate. This natural product contains a novel and unique 11b,12,13,14,15,16-hexahydroazepino[4‘,5‘:2,3]indolo[1,2-c]quinazoline ring system that has not previously been synthesized. We have synthesized 8-desbromohinckdentine A from a 2-aryl indole by first preparing the quaternary center of the natural product and then building the seven-membered lactam and dihydropyrimidine rings onto this intermediate to form the framework of hinckdentine A.
129 citations
TL;DR: In this paper, a Brønsted acidic ionic liquid was used as a catalyst for bis(indolyl)methane derivatives in the presence of catalytic amount of [Msim]Cl under solvent-free conditions at room temperature.
109 citations