Several medicinally important compounds carry a 2-(thiazol-2-yl)guanidine unit. These species are generally (erroneously) represented as 1-(thiazol-2-yl)guanidine species. Quantum chemical studies were performed to identify the appropriate tautomeric state of this class of compounds. B3LYP/6-31+G(d) calculations indicate the preferred tautomeric state of these species is associated with the 2-(thiazol-2-yl)guanidine structure rather than the 1-(thiazol-2-yl)guanidine structure. G2MP2 calculations on the model system were carried out to study the electronic structure, electron delocalization, and protonation energy; MESP, ELF, HOMA, AIM, and NBO analyses were also carried out. The results indicate that this class of compounds may be treated as species with hidden ::N(←L)R character. Upon protonation of the thiazole ring nitrogen, these systems show the electronic structure as in ::N(←L)2(⊕) systems with divalent N(I) oxidation state.

N-(pyridin-2-yl)thiazol-2-amine is a versatile chemical functional unit present in many therapeutically important species. Quantum chemical analysis shows that there are six competitive isomeric structures possible for this class of compounds within a relative energy difference of ∼4 kcal/mol. Some of the isomeric structures possess divalent N(I) character. There appears to be a competition between the thiazole and pyridine groups to accommodate the tautomeric hydrogen, and consequently show electron donating property in the structure with R-N←L representation. Details of electron distribution, tautomeric preferences, protonation energy, and divalent N(I) character, and so on, of this class of compounds are presented in this article. Subsequently, upon protonation, (L→N←L)(⊕) character is clearly evident in these moieties as molecular orbital analysis clearly shows two lone pairs of electrons on the central nitrogen, in this system.

The dative-bond representation (L→E) in compounds with main group elements (E) has triggered extensive debate in the recent past. The scope and limits of this nonclassical coordination bond warrant comprehensive exploration. Particularly compounds with (L→N←L')(+) arrangement are of special interest because of their therapeutic importance. This work reports the design and synthesis of novel chemical species with the general structural formula (L→N←L')(+) carrying the unusual ligand cyclohexa-2,5-diene-4-(diaminomethynyl)-1-ylidene. Four species belonging to the (L→N←L')(+) class carrying this unconventional ligand were synthesized. Quantum chemical and X-ray diffraction analyses showed that the electronic and geometric parameters are consistent with those of already reported divalent N(I) compounds. The molecular orbital analysis, geometric parameters, and spectral data clearly support the L→N and N←L' interactions in these species. The newly identified ligand has the properties of a reactive carbene and high nucleophilicity.

Introduction:Quorum sensing inhibition (QSI) is one of the vital tools to overcome emerging virulence of pathogenic bacteria which aims at curbing bacterial resistance. Targeting QS (quorum sensing) as chemotherapy is less likely to generate resistance among pathogens as it targets only the adaptation and not the survival mechanism of the pathogen. Several QS inhibitors were developed in the recent past but none of them managed to have clinical application due to known toxic effects for human consumption. A rapid development of QS inhibitor drugs could be achieved by verification of the QSI activity of drugs which are already in clinical use with known pharmacology. Recently, a known FDA approved clinical drug niclosamide belonging to an anthelmintic class is found to exhibit QSI activity. Methods: We have focused our study on Albendazole, another FDA approved clinical drug belonging to the same class for its potential to act as QSI. The structure-based molecular docking is used for finding putative interactions made by this drug with the CviR and LasB receptor protein of Chromobacterium violaceum and Pseudomonas aeruginosa , respectively. Further, the in vitro activity of this drug has been evaluated by employing CviR and LasB receptor-based bioassay. The efficacy of this drug alone and in combination with antibiotic Tobramycin to inhibit P. aeruginosa based biofilms was also analyzed by developing the biofilms on chambered glass slides and performing anti-biofilm assay. Results: Further, this drug found to inhibit purple pigment violacein production in C. violaceum , which is under the control of C6-AHL-CviR mediated QS in this human pathogen. The in vivo bioassays results suggested that albendazole has great potential to act as a QS inhibitor as found inhibiting violacein production in C. violaceum and biofilm formation in P. aeruginosa , respectively. Conclusion: It is that structure-based molecular docking guided bioassay evaluation is an efficient tool for finding the new therapeutic use of old drugs which could have more chances to come easily in clinical application for their newly identified therapeutic uses.

In present study a series of 2,4-disubstituted thiazole derivatives was synthesized and evaluated for their in vitro antibacterial and antifungal activities against B. subtilis, E. coli, S. aureus, C. albicans and A. niger by tube dilution method. The analysis of antimicrobial activity results indicated that the presence of NO2 and OCH3 groups at para position of phenyl group improved the antimicrobial activity significantly. Molecular docking studies also supported in vitro activity results and showed that NO2 and OCH3 groups containing compounds have greater affinity towards the target glucosamine-6-phosphate synthase. QSAR studies indicated that molecular connectivity index ( 2 χ v ) and Kier's shape index (α3) are the key parameters for antimicrobial activity of synthesized thiazole derivatives and can be cosidered as important factors for interaction with target site of different microorganisms. It is pertinent to note that multi-target QSAR models were more effectual in demonstrating the antimicrobial activity than one-target QSAR models.