Benzimidazole derivatives as cruzain inhibitors were used in molecular docking and qsar studies. Here we report a structureactivity relationship study of benzimidazolebased compounds that resulted in potent and selective inhibitors of cpimpdh. Insilico molecular design of heterocyclic benzimidazole. Prediction of gas chromatographic retention times and response factors using a general quantitative structure property relationship treatment, anal. Application of qsar models in analysis of antibacterial.
However, with the widespread development of resistance and the availability of more efficient and easier to administer compounds, their use has decreased in ruminants. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against. A structureactivity relationship sar was identified for the benzimidazole thiophenes that held for both somules and adult parasites. Aug 30, 2019 ferreira rs, dessoy ma, pauli i et al. Quantitative structure activity relationship has been used to study the relationships bet. It is a benzimidazole and a polycyclic heteroarene. The rcsb pdb also provides a variety of tools and resources. If the target structure is known, computational chemistry and molecular modelling software packages can be useful in identifying binding site interactions. Structure activity relationship sar studies elucidated a critical role for the n1 nitrogen of both the benzimidazole segment e and urea segment b moieties. Molecular modeling and structureactivity relationships for a. Qsar study and molecular docking of benzimidazole derivatives as.
Molecular modeling and structureactivity relationships. The aim of this study was to test the efficiency of quantitative structure activity relationship qsar and artificial neural networks ann in prediction antiproliferative activity of benzimidazoles. The topscoring enzymeinhibitor complexes were selected for the development of the 3d quantitative structureactivity relationship qsar models and to assess the inhibitor binding modes and intermolecular interactions. Toxicity estimation software tool test safer chemicals. Qsar study of derivatives for antifungal evaluation of. Benzimidazole, a heterocyclic aromatic organic compound consisting of a fusion of benzene and imidazole, in an extension of the wellelaborated imidazole system, has been used as a carbon skeleton for n heterocyclic carbenes, usually used as ligand for transition metal complexes. If the target structure is known, computational chemistry and molecular modelling software. Molecular docking technique is routinely used in modern drug discovery for understanding the drugreceptor interaction. Structure activity relationship sar is an approach to find qualitative relationships between chemical. A preliminary assessment of the structureactivity relationship of benzimidazolebased antiproliferative agents leyte l. A series of substituted 24methoxyphenyl1hbenzimidazoles were synthesized and evaluated as inhibitors of topoisomerase i. However, in recent years, a quantitative structure activity relationship qsar has aroused many researchers interest in the studies of. Benzimidazoles heterocyclic building blocks sigmaaldrich. Synthesis and antimicrobial activity of certain benzimidazole.
Structureactivity relationships of benzothiazole and benzimidazole. Abstract the paper describes a quantitative structureactivity relationship qsar study of ic 50 values of benzimidazole derivatives on escherichia coli methionine aminopeptidase. The tested compounds displayed in vitro inhibitory activity and their minimum inhibitory concentrations were determined. The structural features necessary for cox2 inhibitory activity for a series of oxadiazole substituted benzimidazoles were explored through 3dqsar, combinatorial library generation combi lab and molecular docking. Structure activity relationships sar explore the relationship between a molecules biological activity and the three dimensional structure of the molecule. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. Two types of satisfactory substructurebased 3dqsar models were.
Main focus is on structure activity relationship sar study of benzimidazole scaffold for different biological activities. The in vivo pharmacokinetic pk and efficacy studies on compound 3 are also described. The most prominent benzimidazole complex features nribosyldimethylbenzimidazole as found in vitamin b 12. In the present project, synthesis, pharmacological evaluation, probable mechanism of action and quantitative structure activity relationship qsar of benzmidazole2carboxylic acids are reported. A quantitative structureactivity relationship qsar study has been carried out for a training set. It is a tautomer of a 4h benzimidazole, a 2h benzimidazole and a 3ah benzimidazole. The ligands bind to the ck2 active site in a different way with respect to the parent. Synthesis and structureactivity relationships of imidazolecoumarin. These molecules are visualized, downloaded, and analyzed by users who range from students. May 16, 2017 docking simulations were executed using the crystallographic structure of cruzain in complex with a benzimidazole inhibitor. Comprehensive structure activity relationship studies for angiotensin ii receptor antagonists as antihypertensive. Design and structureactivity relationship of 3benzimidazol. It is a tautomer of a 4hbenzimidazole, a 2hbenzimidazole and a 3ahbenzimidazole.
The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. The structure activity relationship study among the newly synthesized compounds revealed that. Benzoxazole natural products and medicinalagrochemical applications of benzoxazoles. The parent structure of novel benzimidazole and its derivatives which have been used in this study has been presented in the figure 1. Further, the presence of chlorine at 2 nd and methyl at 6 th position of quinolone ring, substituted at 2 nd position of benzimidazole ring, required for. Cellbased assay showed that compounds were active at 1. Quantitative structureactivity relationship qsar has been used to study the. Molecular modeling studies on benzimidazole carboxamide. Structurebioactivity relationship for benzimidazole.
Comprehensive structure activity relationship studies for. A quantitative structure activity relationship qsar has been carried out on a series of benzimidazole derivatives to identify the structural requirements for their. The benzimidazoles are a large chemical family used to treat nematode and trematode infections in domestic animals. Structure activity relationship qsar and quantitative structure property relationship qspr is the field of science. The results are discussed on the basis of statistical data. Synthesis, biological evaluation, and structureactivity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as antitrypanosoma cruzi agents. The whole pharmaceutical activity of the compounds has been decided by the above groups.
Structure activity relationship sar study of benzimidazole scaffold for different biological activities. The structureactivity relationship study among the newly synthesized compounds revealed that. The most potent inhibitors produced marked phenotypic alterations at 12. Glutaminyl cyclase hqc has emerged as a new potential target for the treatment of alzheimers disease ad.
Structure activity relationship sar study of benzimidazole. Structureactivity relationships of benzimidazoles and. Quantitative structure activity relationship qsar analysis was applied to 28 of the. Pdf quantitative structure activity relationship and. In 1991 benzimidazole derivatives were synthesized by derivatization at nh of benzimidazole by electron donating group and substitution with long chain of propyl, acetamido, thio, thiazoleamino, tetramethyl piperidine on pyridine resulting in good antiulcer activity 2,3. At first benzimidazole derivatives were built by hyperchem software and.
Benzimidazole derivatives showed promising antiinflammatory activity through the inhibition of cox2 enzyme. The tested compounds displayed in vitro antifungal activity and minimum inhibitory concentration mic was determined for all the compounds. Molecular modeling, synthesis and biological evaluation of. Jun 05, 2015 structure activity relationship sar study of benzimidazole scaffold for different biological activities. Structure activity relationship sar analysis software programs, such as oncologic and multicase mcase, work by analyzing the chemical structure of a compound of unknown toxicity and predicting its likelihood to be a carcinogen based on comparisons to the structures of compounds with known toxicity and programmed chemical and. Prediction of inhibition performance of some benzimidazole. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Pharmacological compounds of benzimidazole derivatives are potent inhibitors for a variety of. The presence of a 5formyl, 5aminocarbonyl, or 5nitro group i. Qsar study of derivatives for antifungal evaluation of novel. The studies on structureactivity relationship clearly suggested antihiv activity of pyrimidine and benzimidazole derivatives and these findings were consistent with the in vitro cellbased experimental data. Molecular modeling and structureactivity relationships for a series. Novel benzimidazole derived naphthalimide triazoles. Sar tables consist of the compounds, their physical properties, and activities. Quantitative structureactivity relationship qsar has been used to study the relationships between the antifungal activity and lipophilicity parameter, logp, calculated by using cs chemoffice software version 7.
A variety of lipophilicity parameters log p hyper, cs log p, mi log p, a log p, ia log p, c log p, log p kow, and x log p were calculated using different software products, and. Synthesis, antihiv, antimicrobial evaluation and structure activity relationship studies of some novel benzimidazole derivatives. Quantitative structure activity relationship and artificial. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. The imine can be alkylated and also serves as a ligand in coordination chemistry. The antibacterial activity of some substituted benzimidazole derivatives against gram negative bacteria escherichia coli was investigated. The best qsar model for prediction of antifungal activity of the. Herein, we disclose the synthesis, structureactivity relationship sar, and biological assessment of a series of benzimidazole derivatives based on the lead compound 3.
Synthesis, reactions, structureactivity relationship of 2. Antibacterial activity of benzimidazole derivatives. Structureactivity relationship sar studies elucidated a critical role for the n1 nitrogen of both the benzimidazole segment e and urea segment b moieties. The ligands bind to the ck2 active site in a different way with respect to the parent compound tbb. A preliminary assessment of the structure activity relationship of benzimidazole based antiproliferative agents leyte l. The most prominent benzimidazole complex features nribosyldimethylbenzimidazole as. Structureactivity relationships of benzimidazole derivatives as antiparasitic agents. Describes the activity the benzimidazole series studied here against cruzain and trypanosoma cruzi. Docking simulations were executed using the crystallographic structure of cruzain in complex with a benzimidazole inhibitor. Initially, a number of basic amines were surveyed on the d ring to attempt to improve both in vitro potency and solubility. Quantitative structureactivity relationships to predict. Here, the crystal structure of the complexes between ck2 and three selective tetrabromobenzimidazole derivatives inhibiting ck2 with ki values between 40 and 400 nm are presented. Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular.
A data set of 31 benzimidazole derivatives with antibacterial activities against grampositive e. Several compounds display potent antiparasitic activity in vitro. Quantitative structureactivity relationship qsar has been used to study the relationships between inhibitory activity and lipophilicity parameters log p. Structure activity relationship is typically evaluated in a table form, called an sar table. As such it is the concept of linking chemical structure to a chemical property e. As a member of the wwpdb, the rcsb pdb curates and annotates pdb data according to agreed upon standards. Uzelac university of novi sad, faculty of technology, novi sad, serbia abstract in the present study, a quantitative structure activity. The inhibition of hqc prevents of the formation of the a. Structureactivity relationships of benzimidazolebased. In the present paper, the antifungal activity of some 1benzylbenzimidazole derivatives were evaluated against yeast saccharomyces cerevisiae.
Candida albicans activity were used for quantitative structureactivity relationship qsar study. Abstract the paper describes a quantitative structure activity relationship qsar study of ic 50 values of benzimidazole derivatives on escherichia coli methionine aminopeptidase. Structureactivity relationships sar explore the relationship between a molecules biological activity and the three dimensional structure of the molecule. The benzimidazole contains a phenyl ring fused to an imidazole ring, as indicated in the structure for benzimidazole figure 4. The pharmaceutical activity of the compounds due to the function of specific groups that occupied the position of that group or atom or bond or stereo chemical orientation. Abstract benzimidazoles are the fused heterocyclic ring systems which form an integral part of vitamin b 12 and have been luring many researchers all over the world to assess their potential therapeutic significance. Structure activity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied compounds. Inspecting the structureactivity relationship of protein. Synthesis, reactions, structureactivity relationship of 2benzimidazole. An insight into antimicrobial activity substituted benzimidazole derivatives through qsar studies. Benzimidazole derivatives have shown hopeful activity in the treatment of several diseases, for this reason, the synthesis of novel benzimidazole remains a main focus for researchers. Benzimidazole moiety with heteroaryl and psudoacedic nature is promising moiety for development of nsaids. The activity of the 32 inhibitors has been estimated by means of multiple linear regression mlr and artificial neural network ann techniques. Above structure activity relationship concluded that formation of complex between benzimidazole nucleus and co ii led to increase in antimicrobial activity of synthesized compounds.
Quantitative structureactivity relationship has been used to study the relationships bet. The sar results were also supported by the xray crystallographic elucidation of the role of the n1 nitrogen and the urea moiety when the benzimidazole urea compounds were bound to the. Ck2 is a very pleiotropic protein kinase whose high constitutive activity is suspected to cooperate to neoplasia. Application of qsar models in analysis of antibacterial activity of some benzimidazole derivatives against sarcina lutea sanja o. The repo rt and recommendations of ecvam workshop 52. Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity.
1249 527 1236 489 1249 249 790 1153 805 1 669 306 101 122 1497 423 647 534 1463 1175 830 244 733 102 1494 868 1368 361 398 446 535 626 728 453 916 62 156 87 240 18 673