134469-07-1Relevant articles and documents
Synthesis and antitrichinellosis activity of some 2-substituted-[1,3] thiazolo[3,2-a]benzimidazol-3(2H)-ones
Mavrova, Anelia Ts.,Anichina, Kamelya K.,Vuchev, Dimitar I.,Tsenov, Jordan A.,Kondeva, Magdalena S.,Micheva, Mitka K.
, p. 5550 - 5559 (2005)
Some new thiazolo[3,2-a]benzimidazolone derivatives were synthesized using two methods. The structures of the synthesized compounds were proved by means of IR, 1H NMR and mass spectral data. Ab initio computations were performed in order to determine the electronic structure and geometry of the investigated molecules and to compare it to the geometry of albendazole. Biologically, experiments in vitro and in vivo were accomplished in order to identify the efficacy of the obtained thiazolobenzimidazolones against Trichinella spiralis. The effectiveness of compounds 4a-c in the intestinal phase of trichinellosis was 100% and in the muscle phase were 88% and 80% at a concentration of 100 mg/kg mw for the compounds 4a and 4c. The results of the hepatotoxicity test showed that the compounds 4a and 4b possess hepatotoxicity comparable to that of albendazole.
A comparative study of the behavior of cyanothioformamide and oxazolidine (thiones or iminothiones) towards some binucleophiles
El-Sharief,Ammar,Mohamed,El-Gaby
, p. 291 - 298 (2002)
Reactions of cyanothioformamides (I) with o-phenylenediamines, o-aminophenol, and anthranilic acids furnished benzimidazole (II,III), benzoxazole (VII), quinazoline (IX) derivatives, respectively. Oxazolidine (thiones or iminothiones) (IV) were reacted with the same binucleophiles to produce quinoxaline (V), benzimidazole (VI), and quinazoline (XI) derivatives.
Synthesis, characterization, and biological activity of a novel series of benzo[4,5]imidazo[2,1-b]thiazole derivatives as potential epidermal growth factor receptor inhibitors
Deng, Xinshan,Tan, Xiaoyu,An, Tiantian,Ma, Qingqing,Jin, Zhe,Wang, Ce,Meng, Qingguo,Hu, Chun
, (2019)
Based on the analysis of epidermal growth factor receptor (EGFR) complexes with gefitinib with molecular docking, the scaffold-hopping strategy, combination of the active substructures, and structural optimization of EGFR inhibitors, a novel series of benzo[4,5]imidazo[2,1-b]thiazole derivatives was designed, synthesized, and evaluated for antitumor activity in human cancer cell lines and cellular toxicity against human normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and EGFR inhibitory activities in vitro. Some target compounds such as 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(2-hydroxyphenyl)acetamide (D04) and 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(naphthalen-1-yl)acetamide (D08) have shown significant antitumor activity against the EGFR high-expressed human cell line HeLa. All the target compounds showed hardly any antitumor activity against the EGFR low-expressed human cell line HepG2, and nearly no cellular toxicity against the human normal cell lines HL7702 and human umbilical vein endothelial cell lines (HUVEC). The inhibitory activities against EGFR kinase in vitro of the three target compounds were greatly consistent with the anti-proliferative activities. The preliminary structure–activity relationships of the target compounds were summarized. Conclusively, the novel benzo[4,5]imidazo[2,1-b]thiazole derivatives as novel potential EGFR inhibitors may be used as the potential lead compounds for the development of antitumor agents.
Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer
Eisa, Hassan,El-Messery, Shahenda M.,Henen, Morkos A.,Nashaat, Samira
, (2020)
New series of benzimidazole ring core conjugated with either dithiocarbamate or thiopropyl linkers, hybridized with different secondary amines were synthesized; 5–15 and 22–31; respectively. The new compounds were characterized by different spectroscopic techniques (1H, 13C 1D & 2D NMR, ESI-MS and IR). They were screened for in vitro anticancer activity against breast cancer using MCF7 cell line. The results obtained revealed that compounds 5, 12, 15 and 25 were the most active among the synthesized series exhibiting IC50 15N-labeled Pin1 enzyme was conducted using state-of-the-art 2D NMR binding experiments. Results showed promising binding between compounds 5, 12, and 25 by chemical shift perturbation (peak shifting or peak disappearance). Molecular docking study were quite valuable to explain the binding mode of active derivatives via hydrogen bonding. Additional contact preferences and surface mapping studies stated the similarity pattern between active candidates which may pave the way for more precise anti breast cancer target optimization.
Cinnamide derived pyrimidine-benzimidazole hybrids as tubulin inhibitors: Synthesis, in silico and cell growth inhibition studies
Sana, Sravani,Reddy, Velma Ganga,Srinivasa Reddy,Tokala, Ramya,Kumar, Rahul,Bhargava, Suresh K.,Shankaraiah, Nagula
, (2021)
An approach in modern medicinal chemistry to discover novel bioactive compounds is by mimicking diverse complementary pharmacophores. In extension of this strategy, a new class of piperazine-linked cinnamide derivatives of benzimidazole-pyrimidine hybrids have been designed and synthesized. Their in vitro cytotoxicity profiles were explored on selected human cancer cell lines. Specifically, structural comparison of target hybrids with tubulin-DAMA-colchicine and tubulin-nocodazole complexes has exposed a deep position of benzimidazole ring into the αT5 loop. All the synthesized compounds were demonstrated modest to interesting cytotoxicity against different cancer cell lines. The utmost cytotoxicity has shown with an amine linker of benzimidazole-pyrimidine series, with specificity toward A549 (lung cancer) cell line. The most potent compound in this series was 18i, which inhibited cancer cell growth at micromolar concentrations ranging 2.21–7.29 μM. Flow cytometry studies disclosed that 18i inhibited the cells in G2/M phase of cell cycle. The potent antitumor activity of 18i resulted from enhanced microtubule disruption at a similar level as nocodazole on β-tubulin antibody, explored using immunofluorescence staining. The most active compound 18i also inhibited tubulin polymerization with an IC50 of 5.72 ± 0.51 μM. In vitro biological analysis of 18i presented apoptosis induction on A549 cells with triggering of ROS generation and loss of mitochondrial membrane potential, resulting in DNA injury. In addition, 18i displayed impairment in cellular migration and inhibited the colony formation. Notably, the safety profile of most potent compound 18i was revealed by screening against normal human pulmonary epithelial cells (L132: IC50: 69.25 ± 5.95 μM). The detailed binding interactions of 18i with tubulin was investigated by employing molecular docking, superimposition and free energy analyses. Thus remarks made in this study established that pyrimidine-benzimidazole hybrids as a new class of tubulin polymerization inhibitors with significant anticancer activity.
Synthesis, crystal study, and anti-proliferative activity of some 2-benzimidazolylthioacetophenones towards triple-negative breast cancer MDA-MB-468 cells as apoptosis-inducing agents
Abdel-Aziz, Hatem A.,Eldehna, Wagdy M.,Ghabbour, Hazem,Al-Ansary, Ghada H.,Assaf, Areej M.,Al-Dhfyan, Abdullah
, (2016)
On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 μM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 μM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.
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)
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.
Synthesis and antitrichinellosis activity of some bis(benzimidazol-2-yl)amines
Mavrova, Anelia Ts.,Denkova, Pavletta,Tsenov, Yordan A.,Anichina, Kameliya K.,Vutchev, Dimitar I.
, p. 6291 - 6297 (2007)
Novel bis(benzimidazol-2-yl)amines were synthesized using two methods and studied for antitrichinellosis activity. DFT calculations were performed in order to determine the geometry of molecules. All derivatives of 2-aminobenzimidazole exhibited higher activity in vitro against Trichinella spiralis larvae in regard to the activity of albendazole, moreover compounds 4f-i manifested antitrichinellosis effect, which surpassed five times the activity of albendazole. The in vivo screening of intestinal phase of the T. spiralis revealed 100% effectiveness of compounds 4g-i at oral dosages of 50 and 100 mg/kg mw, while albendazole possesses 100% efficacy only at a dose of 100 mg/kg mw.
Synthesis and antibacterial evaluation of some novel mannich bases of benzimidazole derivatives
Ahmadi
, p. 421 - 425 (2016)
Substituted benzimidazoles are known for their chemotherapeutic importance and many pharmacological properties. In this paper, we synthesized some novel Mannich bases of benzimidazole derivatives. The synthesized compounds were characterized by their physical and spectral data and in vitro antibacterial activity of these compounds tested against Bacillus subtilis, Bacillus pumilus, Escherichia coli and Pseudomonas aeruginosa organisms. The potency of the synthesized compounds was determined against standard drug Ciprofloxacin by measuring the zone of inhibition.
Novel and improved method for the synthesis of 2-mercaptobenzimidazole derivatives
El Kihel,Ait Sir,Jebbari,Ahbala,Guesmi,Bauchat
, p. 1765 - 1768 (2016)
2-mercaptobenzimidazole derivatives were synthesized by reaction of o-phenylenediamines with N-aminorhodanine. This reaction represent a new synthesis of 2-mercaptobenzazole. The structure of the obtained products was established by spectroscopic data.
