Indole-based alkaloids are well-known in the literature for their diverse biological properties. Polysubstituted optically active tetrahydro-β-carboline derivatives functionalized on C-1 position are the common structural motif in most of the indole-based alkaloids, as well as highly marketed drugs. The stereoselective Pictet-Spengler reaction is one of the currently most important synthetic techniques used for the preparation of these privileged tetrahydro-β-carboline scaffolds. To date, there are numerous research reports that have been published on the synthesis of the tetrahydro-β-carboline scaffold both on solid phase, as well as in solution phase. Moreover rapid growth has been observed for the enantioselective synthesis of tetrahydro-β-carboline scaffold using chiral organocatalysts. In this Review, efforts have been taken to shed light on the latest information available on different strategies to synthesize tetrahydro-β-carboline both on solid phase and in solution phase during the last 20 years. Furthermore, we believe that the present synthetic methodologies covered in this Review will help to improve the status of this privileged tetrahydro-β-carboline scaffold in its use for drug discovery.
Simultaneous C−N, and N−N bond‐forming methods for one‐pot transformations are highly challenging in synthetic organic chemistry. In this study, the Cu2O rhombic dodecahedra‐catalyzed synthesis of 2H‐indazoles is demonstrated with good to excellent yields from readily available chemicals. This one‐pot procedure involves Cu2O nanoparticle‐catalyzed consecutive C−N, and N−N bond formation followed by cyclization to yield 2H‐indazoles with broad substrate scope and high functional group tolerance. Various cell‐based bioassay studies demonstrated that 2H‐indazoles inhibit the growth of cancer cells, typically through induction of apoptosis in a dose‐dependent manner. Moreover, 2H‐indazoles tested in the MDA‐MB‐468 cell line were capable of inhibiting cancer cell migration and invasion. Thus, it is shown that 2H‐indazoles have potent in vitro anticancer activity that warrant further investigation of this compound class.
Chronic neurological disorder of the brain is the main reason for the disease epilepsy, which affects people of almost all ages. According to World Health Organization estimates, particularly in developing regions of the world nearly 80% of people suffer from different forms of epilepsy. The majority of epileptic seizures are controlled by the use of antiepileptic drugs, which are often associated with related side effects such as blurry vision, fatigue, sleepiness, and stomach upset. Lennox–Gastaut syndrome (LGS) is childhood-onset epilepsy with multiple different types of seizures that impair intellectual development. To treat LGS, Novartis developed an antiepileptic drug known as rufinamide that contains a 1,2,3-triazole ring, and it is manufactured by Eisai under the brand name of Banzel or Inovelon. This review provides a brief background on LGS and summarizes the literature reports on different synthetic routes for rufinamide, which was approved by the U.S. Food and Drug Administration in November 2008.
In this work, we have synthesized a series of novel C,Ncyclometalated 2H-indazole-ruthenium(II) and -iridium(III) complexes with varying substituents (H, CH 3 , isopropyl, and CF 3 ) in the R 4 position of the phenyl ring of the 2H-indazole chelating ligand. All of the complexes were characterized by 1 H, 13 C, high-resolution mass spectrometry, and elemental analysis. The methyl-substituted 2H-indazole-Ir(III) complex was further characterized by single-crystal X-ray analysis. The cytotoxic activity of new ruthenium(II) and iridium(III) compounds has been evaluated in a panel of triple negative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-MB-468) and colon cancer cell line HCT-116 to investigate their structure−activity relationships. Most of these new complexes have shown appreciable activity, comparable to or significantly better than that of cisplatin in TNBC cell lines. R 4 substitution of the phenyl ring of the 2Hindazole ligand with methyl and isopropyl substituents showed increased potency in ruthenium(II) and iridium(III) complexes compared to that of their parent compounds in all cell lines. These novel transition metal-based complexes exhibited high specificity toward cancer cells by inducing alterations in the metabolism and proliferation of cancer cells. In general, iridium complexes are more active than the corresponding ruthenium complexes. The new Ir(III)-2H-indazole complex with an isopropyl substituent induced mitochondrial damage by generating large amounts of reactive oxygen species (ROS), which triggered mitochondrionmediated apoptosis in TNBC cell line MDA-MB-468. Moreover, this complex also induced G2/M phase cell cycle arrest and inhibited cellular migration of TNBC cells. Our findings reveal the key roles of the novel C−N-cyclometalated 2H-indazole-Ir(III) complex to specifically induce toxicity in cancer cell lines through contributing effects of ROS-induced mitochondrial disruption along with chromosomal and mitochondrial DNA target inhibition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.