Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus (original) (raw)
Related papers
SYNTHESIS AND ANTIVIRAL ACTIVITY OF NEW THIAZOLE, 1,2,4-TRIAZOL AND OXINDOLE DERIVATIVES
The synthesis and antiviral activity evaluation of new derivatives of 2-aminothiazole, 1,2,4-triazole, as well as oxindoles has been realized. The synthesized compounds exhibited different cytotoxicity, in particular, oxindols 4 , 5 , 7 , 8 , 9, 10, 11, 12, 13, 58 as well as thiazole/triazole 73 and 75 turned out to be the most cytotoxic for MT-4 cell lines. The compounds 11, 12, 73, and 75 are more toxic than reference compound Efavirenz. As far as the antiviral activity is concerned, none of the title compounds turned out active against Reo-1, Sb-1, VSV, RSV, YFV and VV viruses. The results obtained against Bovine Viral Diarrhoea Virus (BVDV) showed that nine compounds (six from oxindol's seria 6, 12, 13, 52, 56, 58 and three 73, 75, 77 of triazole homologues) resulted moderate active. Among all of them, the most potent compound was 52, with EC 50 of 6.6 μM. Studies of effect of synthesized compounds against Coxsakie Virus (CVB-2) revealed that only two compounds, 13 and 73 exhibit moderate activity (EC 50 >40 and >18 μM, respectively). It should be noticed that eleven compounds, 4, 5, 7, 8, 9, 10, 11, 12, 13, 58, and 75 showed moderate activity against HIV-1 (EC 50 >16 – m >59μM).
Recent Advances in Antiviral Benzimidazole Derivatives: A Mini Review
Pharmaceutical Chemistry Journal, 2019
Benzimidazole ring system is well known for its potential for various biological activities. Recent research works have indicated the excellent antiviral potential of various derivatives of this heterocycle. Depending upon the nature of substitution and side chain functionalities, benzimidazole derivatives exhibit anti-HCV, anti-HBV, anti-HIV, anti-HSV, anti-Coxsackie virus, anti-rotavirus, anti-mosquito larvae, anti-PRSV, anti-adenovirus, anti-tobacco mosaic, and anti-Sunn-hemp rosette viruses, etc. In this article, the recent literature available on antiviral benzimidazole derivatives is summarized. The article could be useful in designing new antiviral agents based on this ring system.
Saudi Pharmaceutical …, 2008
A set of heterocyclic benzimidazole derivatives bearing 1,3,5-triazine group with different substituents at C-2 and C-5 of the benzimidazole ring have been synthesized and evaluated for their antiviral activities against HSV-1. The structures of these compounds have been established by analytical data, IR spectra, 1 H NMR, and mass spectra. Compounds 8a and 8b proved to be the most active antiherpetic agents in this study, at EC 50 % concentrations of 2.9, 3.4 mg/ml, respectively. Computational evaluation of the quantum chemical descriptors such as hydrophobicity (log P), HOMO & LUMO, and the gap energy, were calculated and correlated with the antiviral activity. The tested compounds showed proper degree of hydrophobicity (<0.5 ->5). The HOMO-LUMO gap energy values of the tested compounds are comparable with the observed values for the antiviral drug, Acyclovir.
Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives
European Journal of Medicinal Chemistry, 2015
Treatment of 3-phenyl-1,3-thiazolidin-4-one derivative 1 with phenylisothiocyanate in DMF, in the presence of potassium hydroxide, at room temperature gave the non-isolable potassium salt 2. The insitu reaction of 2 with differently substituted N-aryl hydrazonoyl chlorides 3, 7aed and 14aed afforded the corresponding 2-(pyrazolyl)thiazolylimino-5-(thiadiazolylidene)thiazolidin-4-one derivatives 6, 10a ed and 17aed, respectively. Reaction of 2 with further a-haloketones yielded the 4-(pyrazolyl)thiazolylimino-bis-thiazolidine derivatives 22, 25 and 26. Single crystal X-ray analysis was used in structure elucidation of the products. The in-vitro antiviral screening against four viruses (Poliovirus, Influenza A (H1N1) virus, Hepatitis B virus and Hepatitis C virus) for the obtained compounds was examined. Structure activity relationship (SAR) was also studied. The goal of the work was achieved in discovering a very active compound 10a as anti HCV agent (EC 50 0.56 mM).
Antiviral and Antiproliferative Activity in vitro of some New Benzimidazole Derivatives
Pharmacology & Toxicology, 2001
The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Their antitumour activity against human chronic myeloid leukaemia cells was evaluated and compared with that of equimolar doses of daunorubicin. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus. However, it should be noted that, in the case of hydroxybenzyl-benzimidazole, resistance also builds up to compound 7a, the Coxsackie B5 virus developing resistance to it after about ten runs. Cytotoxicity tests show that many of these substances are well tolerated by the VERO cells. The mechanism of action is still unclear.
Antiviral chemistry & chemotherapy, 2005
To improve anti-helical activity of analogues of 1H-benzotriazole and 1H-benzimidazole their N-alkyl derivatives were synthesized and tested for antihelicase activity against enzymes of selected Flaviviridae including hepatitis C virus (HCV), West Nile virus (WNV), Dengue virus (DENV) and Japanese encephalitis virus (JEV). 1- and 2-alkyl derivatives of 4,5,6,7-tetrabromo-1H-benzotriazole were obtained by direct alkylation of 4,5,6,7-tetrabromo-1H-benzotriazole with the use of respective alkyl halides in the presence of KOH in methanol, to give a mixture of 1- and 2- isomers, which was separated by flash column chromatography in good yield. The proportion of isomers strongly depended on the reaction time and temperature. 1- and 2-hydroxyethyl and 1- and 2-chloroethyl derivatives of the tetrabromobenzo-triazole were synthesized with the use of 2-bromoethanol and 1-bromo-2-chloroethane respectively as alkylating agents. N-alkylation of this benzotriazole compound enhanced inhibitory ac...
Journal of enzyme inhibition and medicinal chemistry, 2015
A novel series of 5-nitro-1H-benzimidazole derivatives substituted at position 1 by heterocyclic rings was synthesized. Cytotoxicity and antiviral activity of the new compounds were tested. Compound 3 was more active than doxorubicin against A-549, HCT-116 and MCF-7. However, compound 3 showed no activity against human liver carcinoma Hep G-2 cell line. Compounds 9 and 17b (E) showed potency near to doxorubicin against the four cell lines. The acute toxicity of compound 9 on liver cancer induced in rats was determined in vivo. Interestingly, it showed restoration activity of liver function and pathology towards normal as compared to the cancer-bearing rats induced by DENA. Compounds 17a (Z), 17b (E) and 18a (Z) were the most promising compounds for their antiviral activity against rotavirus Wa strain.
Research on Chemical Intermediates, 2012
In recent years the synthesis of benzimidazole and its derivatives has attracted the attention of many organic chemists because of the compounds' interesting biological activity and the crucial importance of the benzimidazole unit in the function of these biologically important molecules. Benzimidazole-based polyheterocyclic compounds have several interesting biological properties. Simple synthetic strategies leading to benzimidazole-based fused polyheterocyclic systems and the antiviral and anticancer biological activity of the compounds are surveyed in this review article.