2646-30-2Relevant academic research and scientific papers
Design, synthesis, and antipoliferative activities of novel substituted imidazole-thione linked benzotriazole derivatives
El-Malah, Afaf,Khayyat, Ahdab N.,Malebari, Azizah M.,Mohamed, Khaled O.
, (2021/10/12)
A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, BI9 showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC50 3.57, 0.40 and 2.63 μM, respectively. Compound BI9 was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G2/M phase. Compound BI9 showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound BI9 promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.
Chemical Genetics Reveals a Role of Squalene Synthase in TGFβ Signaling and Cardiomyogenesis
Takemoto, Yasushi,Kadota, Shin,Minami, Itsunari,Otsuka, Shinya,Okuda, Satoshi,Abo, Masahiro,Punzalan, Louvy Lynn,Shen, Yan,Shiba, Yuji,Uesugi, Motonari
supporting information, p. 21824 - 21831 (2021/08/30)
KY02111 is a widely used small molecule that boosts cardiomyogenesis of the mesoderm cells derived from pluripotent stem cells, yet its molecular mechanism of action remains elusive. The present study resolves the initially perplexing effects of KY02111 on Wnt signaling and subsequently identifies squalene synthase (SQS) as a molecular target of KY02111 and its optimized version, KY-I. By disrupting the interaction of SQS with cardiac ER-membrane protein TMEM43, KY02111 impairs TGFβ signaling, but not Wnt signaling, and thereby recapitulates the clinical mutation of TMEM43 that causes arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart disease that involves a substitution of myocardium with fatty tissue. These findings reveal a heretofore undescribed role of SQS in TGFβ signaling and cardiomyogenesis. KY02111 may find its use in ARVC modeling as well as serve as a chemical tool for studying TGFβ/SMAD signaling.
Synthetic (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives as promising chemotherapy agents on cell lines infected with HTLV-1
Chaves, Otávio Augusto,De Oliveira, Thais Silva,Echevarria, Aurea,Echevarria-Lima, Juliana,Netto-Ferreira, José C.,Paiva, Rojane O.,Sousa-Pereira, Danilo
, (2020/06/29)
Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51-7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a-d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a-d is spontaneous and moderate (Ka ～ 104 M-1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.
Synthesis, characterization and catalytic performance of Pd(II) complex immobilized on Fe3O4@SiO2 nanoparticles for the ligand-free cyanation of aryl halides using K4Fe(CN)6
Nasrollahzadeh, Mahmoud,Maryami, Mahboobe,Sajjadi, Mohaddeseh,Mehdipour, Ebrahim
, (2019/03/11)
This work shows the preparation of a novel magnetic catalyst via immobilization of Pd(II)-N-benzyl-N-(4-bromophenyl)-5-amino-1H-tetrazole complex on the Fe3O4@SiO2 nanoparticles (NPs). The application of Fe3O4@SiO2 NPs supported Pd(II)-N-benzyl-N-(4-bromophenyl)-5-amino-1H-tetrazole complex [Fe3O4@SiO2-BAT-Pd(II)] nanocatalyst is described for the cyanation of aryl iodides and bromides to the corresponding aryl nitriles using potassium hexacyanoferrate(II) [K4Fe(CN)6] as a non-toxic and economic cyanating agent under ligand- and additive-free conditions. Some aryl nitriles were efficiently synthesized from the corresponding aryl bromides and iodides in the presence of Fe3O4@SiO2-BAT-Pd(II) nanocomplex. The core-shell nanocomplex demonstrated the superior catalytic performance for the synthesis of synthetically valuable aryl nitriles within good to excellent yields. This process eliminates the need to handle highly toxic metal cyanides, and it can be easily recovered and reused for six consecutive runs with no decreasing of its catalytic capability. Highlights: Preparation of Pd(II) complex immobilized on Fe3O4@SiO2 nanoparticles [Fe3O4@SiO2-BAT-Pd(II) nanocomplex]. Characterization of Fe3O4@SiO2-BAT-Pd(II) nanocomplex using XRD, FT-IR, EDS, VSM, TEM and FESEM analyses. Catalytic cyanation of the various aryl halides with K4Fe(CN)6 under ligand-free conditions. The nanocomplex can be recovered and isolated six times with no significant loss of its catalytic ability.
Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines
Gon?alves, Itamar Luís,Rockenbach, Liliana,Das Neves, Gustavo Machado,G?ethel, Gabriela,Nascimento, Fabiana,Porto Kagami, Luciano,Figueiró, Fabrício,Oliveira De Azambuja, Gabriel,De Fraga Dias, Amanda,Amaro, Andressa,De Souza, Lauro Mera,Da Rocha Pitta, Ivan,Avila, Daiana Silva,Kawano, Daniel Fábio,Garcia, Solange Cristina,Battastini, Ana Maria Oliveira,Eifler-Lima, Vera Lucia
, p. 995 - 1010 (2018/06/27)
An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC50 values of about half that of the IC50 of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.
Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia
Xu, Siyuan,Zhou, Chen,Liu, Rongfeng,Zhu, Qihua,Xu, Yungen,Lan, Fei,Zha, Xiaoming
, p. 4871 - 4880 (2018/09/22)
Histone lysine specific demethylase 1 (LSD1) is overexpressed in diverse hematologic disorders and recognized as a promising target for blood medicines. In this study, molecular docking-based virtual screening united with bioevaluation was utilized to identify novel skeleton of 5-arylidene barbiturate as small-molecule inhibitors of LSD1. Among the synthesized derivatives, 12a exhibited reversible and potent inhibition (IC50 = 0.41 μM) and high selectivity over the MAO-A and MAO-B. Notably, 12a strongly induced differentiation effect on acute promyelocytic leukemia NB4 cell line and distinctly escalated the methylation level on histone 3 lysine 4 (H3K4). Our findings indicate that 5-arylidene barbiturate may represent a new skeleton of LSD1 inhibitors and 12a deserve as a promising agent for the further research.
Phthaloyl Dichloride–DMF Mediated Synthesis of Benzothiazole-based 4-Formylpyrazole Derivatives: Studies on Their Antimicrobial and Antioxidant Activities
Bala, Renu,Kumari, Poonam,Sood, Sumit,Kumar, Vinod,Singh, Nasib,Singh, Karan
, p. 2507 - 2515 (2018/09/25)
Benzothiazole-based pyrazole derivatives prepared by a molecular hybridization approach with an aim to influence the biological activity significantly. Efficient conversion of hydrazones 3a–k derived from their corresponding methyl ketones to 4-formylpyrazoles 4a–k was carried out at 60°C in dioxane, using the Vilsmeier–Haack reagent isolated from phthaloyl dichloride and N,N-dimethylformamide. The newly synthesized compounds 4a–k and hydrazones 3a–k were screened in vitro for their antimicrobial activities using the broth macrodilution method. The compounds 4a–k were also screened for their antioxidant activities using the DPPH radical scavenging assay. Some of the synthesized compounds showed significant antibacterial and antifungal activities as evident from their minimum inhibitory concentrations. Compound 4d showed remarkable antioxidant activity.
Facile synthesis of 1-(4-bromophenyl)-1H-tetrazol-5-amine and related amide derivatives
Yang, Hao,Ouyang, Yifan,Sun, Yutong,Wang, Zhe,Zhu, Xuanli,Tan, Xiaoli,Wang, Hao,Hong, Wei
, p. 581 - 585 (2017/11/14)
An efficient one-pot synthesis of 1-(4-bromophenyl)-1H-tetrazol-5-amine was performed using 4-bromoaniline as the starting material. A novel and widely applicable amidation procedure was then employed, whereby 1-(4-bromophenyl)-1H-tetrazol-5-amine was acylated with different acyl chlorides in the presence of lithium bis(trimethylsilyl)amide as catalyst, for the high-yield synthesis of [1-(4-bromophenyl)-1H-tetrazol-5-yl]amide derivatives.
Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against: Klebsiella pneumoniae
Wang, Rong,Hou, Shuang,Dong, Xiaojing,Chen, Daijie,Shao, Lei,Qian, Liujia,Li, Zhong,Xu, Xiaoyong
supporting information, p. 2060 - 2066 (2017/11/22)
A series of fused bicyclic 2-aminothiazolyl compounds were synthesized and evaluated for their synergistic effects with polymyxin B (PB) against Klebsiella pneumoniae (SIPI-KPN-1712). Some of the synthesized compounds exhibited synergistic activity. When 4 μg ml-1 compound B1 was combined with PB, it showed potent antibacterial activity, achieving 64-fold reduction of the MIC of PB. Furthermore, compound B1 showed prominent synergistic efficacy in both concentration gradient and time-kill curves in vitro. In addition, B1 combined with PB also exhibited synergistic and partial synergistic effect against E. coli (ATCC25922 and its clinical isolates), Acinetobacter baumannii (ATCC19606 and its clinical isolates), and Pseudomonas aeruginosa (Pae-1399).
Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors
Zhang,Xu,Wang,Kang
, p. 3006 - 3016 (2018/02/21)
A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.
