91200-21-4Relevant articles and documents
β-Carboline tethered cinnamoyl 2-aminobenzamides as class I selective HDAC inhibitors: Design, synthesis, biological activities and modelling studies
Godugu, Chandraiah,Kamal, ahmed,Lakshmi Manasa, Kesari,Namballa, Hari Krishna,Shankaraiah, Nagula,Soni, Jay Prakash,anchi, Pratibha
, (2021/11/11)
The effect of β-carboline motif as cap for HDAC inhibitors containing cinnamic acid as linker and benzamides as zinc binding group was examined in this study. A series of β-carboline-cinnamide conjugates have been synthesized and evaluated for their HDAC inhibitory activity and in vitro cytotoxicity against different human cancer cell lines. Almost all the compounds exhibited superior HDAC inhibitory activity than the standard drug Entinostat for in vitro enzymatic assay. Among the tested compounds, 7h displayed a noteworthy potency with an IC50 value of 0.70 ± 0.15 μM against HCT-15 cell line when compared to the standard drug Entinostat (IC50 of 3.87 ± 0.62 μM). The traditional apoptosis assays such as nuclear morphological alterations, AO/EB, DAPI, and Annexin-V/PI staining revealed the antiproliferative activity of 7h while depolarization of mitochondrial membrane potential by JC-1 was observed in dose-dependent manner. Cell cycle analysis also unveiled the typical accumulation of cells in G2M phase and sub-G1/S phase arrest. In addition, immunoblot analysis for compound 7h on HCT-15 indicated selective inhibition of the protein expression of class I HDAC 2 and 3 isoforms. Molecular docking analysis of compound 7h revealed that it can prominent binding with the active pocket of the HDAC 2. These finding suggest that the compound 7h can be a promising lead candidate for further investigation in the development of novel anti-cancer drug potentially inhibiting HDACs.
Discovery and preliminary mechanism of 1-carbamoyl β-carbolines as new antifungal candidates
Sheng, Tao,Kong, Mengmeng,Wang, Yujie,Wu, HuiJun,Gu, Qin,Chuang, Anita Shyying,Li, Shengkun,Gao, Xuewen
, (2021/06/21)
Natural β-carboline alkaloids are ideal models for the discovery of pharmaceutically important entities. Various 1-substituted β-carbolines were synthesized from commercially inexpensive tryptophan and demonstrated significant in vitro antifungal activity against G. graminis. Significantly, compound 4m (EC50 = 0.45 μM) with carboxamide at 1-position displayed the best efficacy and nearly 20 folds enhancement in antifungal potential compared to Silthiopham (EC50 = 8.95 μM). Moreover, compounds 6, 7, and 4i exhibited excellent in vitro antifungal activities and in vivo protective and curative activities against B. cinerea and F. graminearum. Preliminary mechanism studies revealed that compound 4m caused reactive oxygen species accumulation, cell membrane destruction, and deregulation of histone acetylation. These findings indicated that 1-carbamoyl β-carboline can be selected as a promising model for the discovery of novel and broad-spectrum fungicide candidates.
Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their in Vitro Characterization and in Vivo Analgesic Activities
Bertamino, Alessia,Ostacolo, Carmine,Medina, Alicia,Di Sarno, Veronica,Lauro, Gianluigi,Ciaglia, Tania,Vestuto, Vincenzo,Pepe, Giacomo,Basilicata, Manuela Giovanna,Musella, Simona,Smaldone, Gerardina,Cristiano, Claudia,Gonzalez-Rodriguez, Sara,Fernandez-Carvajal, Asia,Bifulco, Giuseppe,Campiglia, Pietro,Gomez-Monterrey, Isabel,Russo, Roberto
, p. 9672 - 9694 (2020/10/19)
Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, a series of conformationally restricted derivatives of the previously described TRPM8 antagonist N,N′-dibenzyl
