27231-36-3Relevant academic research and scientific papers
A new series of benzoxazole-based SIRT1 modulators for targeted therapy of non-small-cell lung cancer
Sever, Belgin,Akal?n ?ift?i, Gül?en,Alt?ntop, Mehlika Dilek
, (2020/09/21)
In an attempt to identify potential anticancer agents for non-small-cell lung cancer (NSCLC) targeting sirtuin 1 (SIRT1), the synthesis of a new series of benzoxazoles (3a – i) was carried out through a facile and versatile synthetic route. The compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cells using the MTT assay. 2-[(5-Nitro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3e) and 2-[(5-chloro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3g) were the most potent and selective anticancer agents in this series against the A549 cell line, with IC50 values of 46.66 ± 11.54 and 55.00 ± 5.00 μM, respectively. The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. Both compounds induced apoptosis in a dose-dependent manner. The effects of compounds 3e and 3g on SIRT1 activity were determined. On the basis of in vitro studies, it was observed that compound 3g caused a significant decrease in SIRT1 levels in a dose-dependent manner, whereas compound 3e increased the SIRT1 levels. According to molecular docking studies, the substantial alteration in the type of action could be attributed to the difference between the interactions of compounds 3e and 3g with the same residues in the active site of SIRT1 (PDB code: 4IG9). On the basis of in silico ADME (absorption, distribution, metabolism, and excretion) studies, these compounds are predicted to possess favorable ADME profiles. According to the in vitro and in silico studies, compounds 3e and 3g, small-molecule SIRT1 modulators, were identified as potential orally bioavailable anticancer agents for the targeted therapy of NSCLC.
Highly Diastereoselective Synthesis of Dihydro-benzoimidazo-[1,3]-thiazines via Electro-oxidative Selenocyclization of Thioallyl Benzoimidazoles
Halder, Atreyee,Mahanty, Kingshuk,Maiti, Debabrata,De Sarkar, Suman
supporting information, p. 3895 - 3899 (2021/10/23)
The current methodology reveals a green and proficient electro-oxidative tandem selenocyclization of thioallyl benzoimidazoles manufacturing selenylated dihydro-benzoimidazo-thiazine derivatives. Both C?Se and C?N bond formation were achieved via this mild protocol which exhibits good functional group tolerability affording an extensive range of substrate scope up to 96% isolated yields. Complete control over the regioselective formation of the six-membered heterocycle and stereoselective construction of the contiguous stereocenters was established. The practical electrochemical method operates in an undivided cell at ambient temperature without using any metal and external chemical oxidant.
A new strategy for the synthesis of 2-mercaptobenzazole derivatives by green chemistry metrics
Vessally, Esmail,Monfared, Aazam,Eskandari, Zahra,Abdoli, Morteza,Hosseinian, Akram
supporting information, p. 1 - 5 (2020/08/25)
A green and efficient method has been developed for the synthesis of 2-mercaptobenzazole derivatives via the reaction of commercially available aniline derivatives with low-cost and nontoxic potassium thiocyanate in water. The reactions proceeded smoothly under catalyst- and ligand-free conditions to give the corresponding products in good to excellent yields. The versatility, low cost, and environmental friendliness, in combination with high yields and easy work-up makes the procedure noteworthy.
Design, synthesis, and evaluation of different scaffold derivatives against NS2B-NS3 protease of dengue virus
Ganji, Lata R.,Gandhi, Lekha,Musturi, Venkataramana,Kanyalkar, Meena A.
, p. 285 - 301 (2020/11/19)
The number of deaths or critical health issues is a threat in the infection caused by Dengue virus, which complicates the situation, as only symptomatic treatment is the current solution. In this regard we have targeted the dengue protease NS2B-NS3 that is responsible for the replication. The series was designed with the help of molecular modeling approach using docking protocols. The series comprised of different scaffolds viz. cinnamic acid analogs (CA1–CA11), chalcone (C1–C10) and their molecular hybrids (Lik1–Lik10), analogs of benzimidazole (BZ1-BZ5), mercaptobenzimidazole (BS1-BS4), and phenylsulfanylmethylbenzimidazole (PS1-PS4). Virtual screening of various natural phytoconstituents was employed to determine the interactions of designed analogs with the residues of catalytic triad in the active site of NS2B-NS3. We have further synthesized the selected leads. The synthesized analogs were evaluated for the cytotoxicity and NS2B-NS3 protease inhibition activity and compared with known anti-dengue natural phytoconstituent quercetin as the standard. CA2, BZ1, and BS2 were found to be more potent and efficacious than the standard quercetin as evident from the protease inhibition assay.
AlCl3-Promoted Synthesis of 2-Mercapto Benzoheterocycles by Using Sodium Dimethyldithiocarbamate as Thiocarbonyl Surrogate
Liu, Xing,Zhang, Shi-Bo,Dong, Zhi-Bing
, p. 5406 - 5411 (2018/10/20)
A simple, expeditious and high-efficiency synthetic method for the AlCl3-mediated one-pot preparation of 2-mercapto benzoheterocycles (2-mercapto benzothiazoles, benzoxazoles and benzimidazoles) is described. By the treatment of a series of S, O and N heteroatoms containing bifunctional molecules with sodium dimethyldithiocarbamate in AlCl3, the desired benzoheterocycles are obtained smoothly. The protocol can also be applied on the synthesis of a series of thiazolidine-2-thiones, imidazolidine-2-thiones. This novel synthetic approach has advantages such as ligand-free, high efficiency, short reaction time, readily available starting materials and simple experimental procedures.
A catalyst-free and additive-free method for the synthesis of benzothiazolethiones from: O -iodoanilines, DMSO and potassium sulfide
Zhu, Xiaoming,Li, Wenguang,Luo, Xiai,Deng, Guobo,Liang, Yun,Liu, Jianbing
supporting information, p. 1970 - 1974 (2018/05/23)
Under catalyst-free and additive-free conditions, a novel, convenient, eco-friendly method for the synthesis of benzothiazolethiones has been developed. The three-component reaction of o-iodoanilines and K2S with DMSO proceeded smoothly and the corresponding benzothiazolethiones were obtained with good isolated yields. Meanwhile, this method could be used for the synthesis of thioureas from primary diamines. Furthermore, mechanism research showed that DMSO not only functioned as a carbon source, but also as a mild oxidant in this reaction.
Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
, p. 6289 - 6304 (2017/08/02)
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
Tautomerism and isomerism in some antitrichinellosis active benzimidazoles: Morphological study in polarized light, quantum chemical computations
Anichina, Kameliya,Mavrova, Anelia,Yancheva, Denitsa,Tsenov, Jordan,Dimitrov, Rasho
, p. 179 - 187 (2017/09/05)
The morphology of the crystal structure of some antitrichinellosis active benzimidazole derivatives including (1H-benzimidazol-2-ylthio)acetic acids, [1,3]thiazolo[3,2-a]benzimidazol-3(2H)-ones, 1H-benzimidazol-2-ylthioacetylpiperazines and starting 2-mercapto benzimidazoles, was studied by the use of Polarized Light Microscopy (PLM). Characterization of the crystal phase was complimented by Differential scanning calorimetry analysis (DSC) and spectroscopic data. DFT computations were performed in order to investigate the prototropic tautomerism and the geometry of the molecule of the synthesized compounds. One distinct type of crystal structure for each one of 5 or 6-methyl-(1H-benzimidazol-2-ylthio)acetic acid 6 was observed by PLM – dendritic and needle-shaped formations. Compound 14, containing a methyl substituent in the benzimidazole ring crystallized also into two phases; while for the unsubstituted compound 13 a separation of phases does not take place. The influence of the both solvents - chloroform and ethanol on the phase separation and the formation of the crystalline structure of compound 14 was investigated. The morphological study showed that the cyclization of 6 in the presence of acetic anhydride in pyridine medium led to a mixture of 6-methyl-[1,3]tiazolo[3,2-a]benzimidazol-3(2H)-one (10a) and 7-methyl-[1,3]thiazolo[3,2-a]-benzimidazole-3(2H)-one (10b), which crystallized in the form of fibrils and spherulites respectively. It was found that a difference in the crystal structures of substituted and unsubstituted benzimidazol-2-thiones, respectively benzimidazol-2-thiol derivatives exists, which may be due not only to the thiol-thione tautomerism but to the prototropic properties of the hydrogen atom in first position of the ring. The calculation results indicated that the thione form is more stable than the thiol tautomer by 51–55 kJ mol?1. But at the same time ΔG for the two thiol tautomers is below 0.5 kJ mol?1. In solid phase the 5(6)-substituted-1H-benzimidazol-2-thiols crystallized in two different crystal structures while the unsubstituted 1H-benzimidazol-2-thiol possess one type of crystal structure.
An environmentally benign and efficient synthesis of substituted benzothiazole-2-thiols, benzoxazole-2-thiols, and benzimidazoline-2-thiones in water
Liu, Xing,Liu, Min,Xu, Wan,Zeng, Meng-Tian,Zhu, Hui,Chang, Cai-Zhu,Dong, Zhi-Bing
, p. 5591 - 5598 (2017/12/06)
An efficient and practical method for the one-step synthesis of benzothiazole-2-thiols, benzoxazole-2-thiols and benzimidazoline-2-thiones by cyclization of 2-aminothiophenols, 2-aminophenols, and 1,2-phenylenediamines with tetramethylthiuram disulfide (TMTD) in water was described. The features of this method include metal/ligand-free, excellent yield, short reaction time and broad substrate scope. The method provides a facile and convenient preparation of some potentially biologically active compounds.
