79815-18-2Relevant articles and documents
Structure-based discovery of (S)-2-amino-6-(4-fluorobenzyl)-5,6,11,11a-tetrahydro-1H-imidazo[1′,5′:1,6]pyrido[3,4-b]indole-1,3(2H)-dione as low nanomolar, orally bioavailable autotaxin inhibitor
Roy, Ashis,Sarkar, Tonmoy,Datta, Sebak,Maiti, Arup,Chakrabarti, Monali,Mondal, Trisha,Mondal, Chaitali,Banerjee, Apurba,Roy, Subhasis,Mukherjee, Soumen,Muley, Pragati,Chakraborty, Sabyasachi,Banerjee, Manish,Kundu, Mrinalkanti,Roy, Kuldeep K.
, p. 496 - 503 (2022/01/08)
Inhibition of extracellular secreted enzyme autotaxin (ATX) represents an attractive strategy for the development of new therapeutics to treat various diseases and a few inhibitors entered in clinical trials. We herein describe structure-based design, syn
TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: Facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline
Sathish, Manda,Sakla, Akash P.,Nachtigall, Fabiane M.,Santos, Leonardo S.,Shankaraiah, Nagula
, p. 16537 - 16546 (2021/05/19)
Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.
Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents
Hu, Xu,Gao, Xiang,Gao, Gang,Wang, Yanbing,Cao, Hao,Li, Dahong,Hua, Huiming
, (2021/04/02)
The cytotoxicity properties of the β-carboline alkaloids have been broadly investigated. However, the potential application of β-carbolines was hindered due to the moderate activity in cancer. In the present study, thirty β-carboline-(phenylsulfonyl)furoxan hybrids (11a–j, 12a–j and 13a–j) were designed and synthesized through esterification and amidation reaction strategy, and their inhibitory activities against the human breast cancer cell lines MCF-7 and MDA-MB-231 were evaluated by CCK-8 assay. Biological evaluation presented that the most promising amide derivative 13h, substituted with p-methoxyphenyl group at position 1, generated high concentration of NO and evidently depressed the MCF-7 (IC50 = 0.89 μM) and MDA-MB-231 (IC50 = 0.62 μM) cells proliferation. Particularly, the wound healing and transwell assays demonstrated that 13h significantly inhibited the migration and invasion of MDA-MB-231cells. Furthermore, the preliminary mechanisms studies indicated that 13h induced G2/M phase arrest and apoptosis possibly causing by ROS accumulation and ROS-mediated DNA damage. Based on these considerations, 13h may be a promising antimetastatic agent for breast cancer, which is noteworthy for further exploration.
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.
Nanoparticles of a new small-molecule P-selectin inhibitor attenuate thrombosis, inflammation, and tumor growth in two animal models
Feng, Qiqi,Wang, Mengyang,Muhtar, Eldar,Wang, Yaonan,Zhu, Haimei
, p. 5777 - 5795 (2021/09/03)
Purpose: To assess whether the newly designed small-molecule oral P-selectin inhibitor 3S-1,2,3,4-tetrahydro-β-carboline-3-methyl aspartyl ester (THCMA) as a nanomedicine enhances antithrombosis, anti-inflammation, and antitumor activity more than the clinical trial drug PSI-697. Methods: THCMA was designed as an amphiphile containing pharmacophores of PSI-697. Its nanofeatures were explored with TEM, SEM, Tyndall effect, ζ-potential, FT-ICR-MS, and NOESY 2D1H NMR. The P-selectin inhibitory effect of THCMA was demonstrated with molecular docking, ultraviolet (UV) spectra, and competitive ELISA. In vivo and in vitro assays — anti-arterial thrombosis, anti–venous thrombosis, anti-inflammation, antitumor growth, anti–platelet aggregation, rat-tail bleeding time, anticoagulation index, soluble P-selectin (sP-selectin) expression, and serum TNFα expression — were performed to explore bioactivity and potential mechanisms. Water solubility of THCMA was measured using UV-absorption spectra. Results: THCMA self-assembled into nanorings of approximately 100 nm in diameter. Its water solubility was about 1,030-fold that of PSI-697. THCMA exhibited more potent P-selectin inhibitory effect than PSI-697. The oral efficacy of THCMA was 100-fold that of PSI-697 in inhibiting arterial and venous thrombosis and tenfold in inhibiting inflamma-tion. THCMA inhibited thrombosis at a dose that produces no coagulation disorders and no bleeding risk. THCMA exhibited enhanced antitumor activity over PSI-697 without systemic chemotherapy toxicity. THCMA significantly inhibited platelet aggregation in vitro and downregulated the expression levels of serum sP-selectin and TNFα in vivo. Conclusion: A new small-molecule P-selectin inhibitor, THCMA, has been successfully designed as a nanomedicine with largely enhanced oral efficacy compared to the clinical trial drug PSI-697, and thus might be developed for the oral treatment of arterial thrombosis, venous thrombosis, inflammation, and cancer-associated thrombosis.
Design and synthesis of β-carboline derivatives with nitrogen mustard moieties against breast cancer
Bai, Jiao,Cao, Hao,Hu, Xu,Hua, Huiming,Li, Dahong,Sun, Jianan,Wang, Jiesen,Wang, Xinyan
, (2021/08/09)
To discover the promising antitumor agents, a series of β-carboline derivatives with nitrogen mustard moieties were designed and synthesized. Most target derivatives showed antiproliferative activity against MCF-7 and MDA-MB-231 cells. Among them, (1-meth
NITROGEN-CONTAINING COMPOUND, METHOD FOR MANUFACTURING THE SAME, AND OPTICAL FUNCTIONAL MATERIAL INCLUDING THE SAME
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, (2021/08/21)
PROBLEM TO BE SOLVED: To provide a novel nitrogen-containing compound having luminescence property. SOLUTION: A nitrogen-containing compound represented by the following formula (I) in which RA, RB, R1, R2, R3, R4, and X are either one of the following (1) and (2). SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
A class β . Preparation method and anti-tumor application
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, (2021/09/22)
The invention discloses β -carbofuran mustard derivatives as well as a preparation method and application thereof, and belongs to the field of natural medicines and medicinal chemistry. The invention specifically relates to a preparation method of a serie
Novel multifunctional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection
Chauthong, Nattapong,Jiaranaikulwanitch, Jutamas,Jiranusornkul, Supat,Nilkosol, Supitcha,Pandith, Hataichanok,Tadtong, Sarin,Thammarat, Phanit,Vajragupta, Opa
supporting information, (2021/06/15)
Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD is projected to reach 152 million by 2050. Donepezil, rivastigmine, galantamine, and memantine are the only four drugs currently approved by the United States Food and Drug Administration for AD treatment. However, these drugs can only alleviate AD symptoms. Thus, this research focuses on the discovery of novel lead compounds that possess multitarget regulation of AD etiopathology relating to amyloid cascade. The ascorbic acid structure has been designated as a core functional domain due to several characteristics, including antioxidant activities, amyloid aggregation inhibition, and the ability to be transported to the brain and neurons. Multifunctional ascorbic derivatives were synthesized by copper (I)-catalyzed azide–alkyne cycloaddition reaction (click chemistry). The in vitro and cell-based assays showed that compounds 2c and 5c exhibited prominent multifunctional activities as beta-secretase 1 inhibitors, amyloid aggregation inhibitors, and antioxidant, neuroprotectant, and anti-inflammatory agents. Significant changes in activities promoting neuroprotection and anti-inflammation were observed at a considerably low concentration at a nanomolar level. Moreover, an in silico study showed that compounds 2c and 5c were capable of being permeated across the blood–brain barrier by sodium-dependent vitamin C transporter-2.
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
