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.
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Lukovnikov et al.
, p. 908,912 (1963)
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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.
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.
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 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.
Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
, p. 1057 - 1072 (2020)
Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
Homogeneous reaction of carbon disulfide and o-phenylene diamine catalyzed by tertiary amines
Wang, Maw-Ling,Liu, Biing-Lang
, p. 885 - 892 (1996)
Synthesis of 2-mercaptobenzimidazoIe (MBI) was carried out by reacting o-phenylene diamine and carbon disulfide catalyzed by tertiary amine (R3N) in a homogeneous solution. Dichloromethane, chlorobenzene, chloroform, toluene, and benzene were employed as the organic solvent. The advantage of using such organic solvents is that MBI precipitates from the organic solution. Only mechanical separation processes, such as filtration and centrifugation, can be used to obtain the MBI product of high purity. Based on the reaction mechanism, a kinetic model, which included two steps of reactions in the organic phase, was proposed, i.e.: (i) a chemical equilibrium of the reaction of CS2 and R3N to produce an active intermediate (R3N - CS2) was built up within a short period of time and (ii) this active intermediate further reacted with o-phenylene diamine to produce the desired MBI product. A combination of the zeroth order and pseudo-first-order rates law was used to describe the kinetic data. However, the reaction follows pseudo-first-order rate law at higher temperature, and the reaction follows zeroth-order rate law at lower temperature. The effects of the operating conditions on the conversion of o-phenylene diamine were also investigated.
New tilomisole-based benzimidazothiazole derivatives as anti-inflammatory agents: Synthesis, in vivo, in vitro evaluation, and in silico studies
Abdel-Aziz, Hatem A.,Abdelrahman, Rehab S.,Darwish, Sara A.,El-Kerdawy, Mohamed M.,Elsheakh, Ahmad R.,Ghaly, Mariam A.,Hassan, Ghada S.,Shaldam, Moataz A.
, (2022/02/03)
New tilomisole-based benzimidazothiazole derivatives were designed and synthesized in this work. Their anti-inflammatory activity was assessed through the in vivo carrageenan rat paw edema model, and the in vitro COX inhibition assay. Compounds 13, 20, 30
New 1H-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity
Argirova, Maria A.,Georgieva, Miglena K.,Hristova-Avakumova, Nadya G.,Vuchev, Dimitar I.,Popova-Daskalova, Galya V.,Anichina, Kameliya K.,Yancheva, Denitsa Y.
, p. 39848 - 39868 (2021/12/31)
Parasitic infections, caused mainly by the speciesTrichinella spiralis(T. spiralis), are widespread around the world and lead to morbidity and mortality in the population. Meanwhile, some studies have showed that these parasites induce oxidative stress in the infected host. With the aim of developing a class of compounds combining anthelmintic with antioxidant properties, a series of new benzimidazolyl-2-hydrazones5a-l, bearing hydroxyl- and methoxy-groups, were synthesized. The anthelmintic activity on encapsulatedT. spiraliswas studiedin vitrothus indicating that all hydrazones were more active than the clinically used anthelmintic drugs albendazole and ivermectin.5band5dkilled the total parasitic larvae (100% effectiveness) after 24 hours incubation period at 37 °C in both concentrations (50 and 100 μg ml?1). The antioxidant activity of the target compounds was elucidatedin vitroagainst stable free radicals DPPH and ABTS as well as iron induced oxidative damage in model systems containing biologically relevant molecules lecithin and deoxyribose. The two 2,3- and 3,4-dihydroxy hydrazones5band5dwere the most effective radical scavengers in all studied systems. DFT calculations were applied to calculate the reaction enthalpies in polar and nonpolar medium and estimate the preferred mechanism of antioxidant activity. The relative radical scavenging ability of compounds5a-lshowed a good correlation to the experimentally observed trends. It was found that the studied compounds are capable to react with various free radicals - ˙OCH3, ˙OOH and ˙OOCH3, through several possible reaction pathways - HAT in nonpolar medium, SPLET in polar medium and RAF in both media.
