Synthesis, Molecular Docking and Biological Evaluation of 2- Mercaptomidazoles using Solid Phase Synthesis.

BACKGROUND: With the increasing resistance and side effects caused due to antifungal agents there is an urgent need for the new potent antifungal agents with low toxicity profile. Imidazoles have been used against fungal infections since long time. Further, our previous studies demonstrated that mercaptoimidazoles possessed good antifungal potency. AIM AND OBJECTIVE: This study was aimed to study the antifungal potency of new series of 2- mercaptoimidazoles. MATERIALS AND METHODS: Eighteen new 2-mercaptoimidazoles containing substituted phenyl group were synthesized and structures of the synthesized compounds were characterized by spectral studies. The synthesized compounds were screened for their antifungal potency. Compound 2-(1-(3-hydroxyphenyl)-2- mercapto-1H-imidazol-4-yl)phenol was found to be the most potent compound among all synthesized compounds against tested fungal strains. Moreover, all the synthesized compounds were further subjected to molecular docking study for the inhibition of enzyme 14α-demethylase. RESULTS: The in-silico molecular docking study results showed that all the synthesized compounds have minimum binding energy and good affinity for the active site and may be considered as good inhibitor of 14α-demethylase. CONCLUSION: 2-mercaptoimidazoles may be used as potential lead molecules as 14α-demethylase inhibitors.

Molecular Modeling Investigation of Some New 2-mercaptoimidazoles.

BACKGROUND: Docking study has become an important and interesting tool for the investigation of drug- receptor interaction. Computational methodologies have become a crucial component in the drug discovery programs which involves identification of target and lead along with their ADME and pharmacokinetic studies so as to obtain a potent lead. OBJECTIVE: Synthesis and Molecular modeling investigation of some new 2-mercaptoimidazoles. METHOD: New 2- mercaptoimidazoles were synthesized via solid phase synthesis and were characterized by spectral studies i.e IR, 1NMR, Mass spectra and LC-MS. Compounds were screened for their antimicrobial potency via agar well diffusion assay against three bacterial strains and two fungal strains. Compounds were subjected to molecular docking studies for rationalization of their mode of action. RESULTS: 18 new imidazole derivatives having mercapto group (4a-r) were synthesized via solid phase synthesis and were characterized by spectral studies i.e IR, 1NMR, Mass spectra and LC-MS. All the compounds were found to possess promising antimicrobial potency. However, compounds 4j and 4k were found to be the most potent compounds of the series against al the tested strains. The in silcio molecular modeling study results indicated that all the compounds exhibited good affinity towards the active site and thus may be considered as good inhibitors of enzyme 14α.-demethylase. CONCLUSION: Thus, it may be concluded that the compounds are good inhibitors of enzyme 14α.- demethylase and may be further investigated to obtain antimicrobial lead.

Synthesis and antidiabetic activity of 2,4-thiazolidindione, imidazolidinedione and 2-thioxo-imidazolidine-4-one derivatives bearing 6-methyl chromonyl pharmacophore.

Numerous compounds have been prepared in order to improve the pharmacological profile of insulinotropic activities. In the present paper, we report the synthesis and the in vitro insulin releasing activity of the 6-methyl-chromonyl-2,4-thiazolidinediones (IIIa-c, IVa-c, Va-c). Compounds IIIb, IIIc, IVa-c, Va and Vc (at lower concentration; 0.001 mg/mL) were able to increase insulin release in the presence of 5.6 mmol/L glucose. In this series, the most potent compound is IVa having methyl group at N3 position of TZD ring.

Rhenium(I) tricarbonyl complexes with poly(azolyl)borates generated in situ from an organometallic precursor containing the B-H...Re coordination motif.

Complex fac-[Re(kappa(3)-H(mu-H)(2)B(tim(Me)))(CO)(3)] (1) reacts with protic azoles, like 2-mercapto-1-methylimidazole (tim(Me)H), 2-mercaptobenzothiazole (bztH), or pyrazoles (pz*H), to afford fac-[Re(kappa(3)-H(mu-H)B(tim(Me))(2)(CO)(3)] (2), fac-[Re(kappa(3)-H(mu-H)B(tim(Me))(bzt))(CO)(3)] (3), fac-[Re(kappa(3)-H(mu-H)B(tim(Me))(pz))(CO)(3)] (4), fac-[Re(kappa(3)-HB(tim(Me))(pz)(2))(CO)(3)] (5), and fac-[Re(kappa(3)-H(mu-H)B(tim(Me))(3,5-Me(2)-4-EtOOCCH(2)pz))(CO)(3)] (6). Complexes 2-6 are stabilized by tridentate poly(azolyl)borates generated in situ, and their formation involves most probably a metal-assisted process which is considerably faster for the pyrazole derivatives. The characterization of the novel complexes, 3-6, has been done by common analytical techniques, including single crystal X-ray diffraction analysis. The solid state structures confirmed the presence of hybrid heteroscopionates, presenting (kappa(3)-H, S, S'), (kappa(3)-H, S, N), or (kappa(3)-S, N, N) binding motifs. Multinuclear ((1)H, (13)C, and (11)B) NMR studies have also shown that the coordination mode found in the solid state is retained in solution.

Sono-synthesis of imidazolidine-2-thione as a base compound of some pharmaceutical products.

This work describes the results of investigations carried out to investigate the synthesis of imidazolidine-2-thione as a heterocyclic compound in the presence of ultrasound (sono-synthesis) and in the absence of ultrasound (conventional method). Instead of reflux in the conventional method, the mixture was sonicated indirectly in sono-synthetic method with 500 kHz at different temperatures. Some experiments were also carried out without catalyst with 500 and 900 kHz. In the conventional method, the yield of the reaction was increased by increasing the temperature but in sono-synthetic method, the thermal dependence was different in the range of temperature studied (10-50 degrees C). In the presence of ultrasound, the yield was reached to more than 93% after 1h but in the conventional method it reached only 27% under the same conditions. Comparison was carried out with and without catalyst. It is also possible to achieve a high yield of product under sonication without the use of a catalyst.

2-Mercaptoimidazoles, a new class of potent CCR2 antagonists.

We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1 induced Ca-flux below 0.01 microM.

[Synthesis and structure of substituted bromo and nitrobenzyl benzylidene imidazolidinediones and thiazolidinediones]. / Synthèse et structure des bromo et nitrobenzyl benzylidène imidazolidinediones et thiazolidinediones substituées.

Synthesis and physico-chemical properties of five bromobenzyl-benzylidene-imidazolidinediones and five nitrobenzyl- or benzyl-benzylidene-thiazolidinediones are described. The microbiological activity of bromobenzyl-benzylidene-imidazolidinediones against microorganisms such as Candida albicans, Neurospora crassa and Mycobacterium smegmatis are evaluated.

1-Phenyl-5-vinyl-2-imidazolidinethione, a proposed causative agent of Spanish toxic oil syndrome: synthesis, and identification in one of a group of case-associated oil samples.

A method is described for the synthesis and characterization of N-(2-hydroxy-3-butenyl)-N'-phenylthiourea, and its cyclization product, 1-phenyl-5-vinyl-2-imidazolidinethione (PVIZT). Fourteen coded oil samples associated with toxic oil syndrome cases in Spain were examined by gas chromatography-electron impact mass spectrometry for the presence of PVIZT. Although these samples were obtained from households where cases of toxic oil syndrome had been recorded, they differed extremely with regard to their anilide and sulphur contents. In one sample PVIZT was detected at an estimated concentration of 1 mg/kg.

Syntheses and pharmacological activity of substituted imidazolidinethiones and thiomidazolines.

A series of imidazolidinethiones and thioimidazolines was synthesized and tested for their effects on both forced and spontaneous motor activity as well as for their ability to raise the convulsion threshold. The proton NMR spectra for the thioimidazolines synthesized were unusual in that they showed a sharp singlet for the ring ethylene unit rather than the expected A2B2 pattern. The thioimidazolines, 5 and 7, were the most active CNS depressants and had the highest safety index. Significantly, the isomeric imidazolidinethiones, 8 and 9, were comparatively much less effective while being considerably more toxic.