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Sonochemistry under controlled conditions has proven effective in medicinal chemistry and drug development. It can substantially shorten reaction timelines from days or hours to minutes. A convenient one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives catalyzed by PTSA and benzenesulfonic acid in ethanol as solvent, under ultrasonic irradiation and without ultrasound irradiation at 50° C has been achieved successfully. These 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives synthesis were also accomplished using different solvents viz., Methanol, Ethanol, DCM, DMF, Acetonitrile and THF and PTSA as the catalyst. This method yielded the highest % synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives with PTSA as the catalyst in solvent ethanol. These reactions were also optimized for % of PTSA catalyst required to obtain the maximum yield of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives with and without ultrasound irradiation at 50° C. Synthesis of 2,4,5-trisubstituted Imidazole derivatives reaction follows first-order rate kinetics while that of 1,2,4,5-tetrasubstituted Imidazole derivatives reaction follows the second-order rate kinetics. Furthermore, sonochemistry has higher yields, lower cost, easier workups, and higher purity than conventional thermal organic synthesis, which has lower yields, tedious workups, longer reaction periods, lower purity, and numerous byproducts. [ABSTRACT FROM AUTHOR]

We created thiazole and oxazole analogues of diaminopimelic acid (DAP) by replacing its carboxyl groups and substituting sulphur for the central carbon atom. Toxicity, ADME, molecular docking, and in vitro antimicrobial studies of the synthesized compounds were carried out. These compounds displayed significant antibacterial efficacy, with MICs of 70–80 µg/mL against all tested bacteria. Comparative values of the MIC, MBC, and ZOI of the synthesized compound were noticed when compared with ciprofloxacin. At 200 µg/mL, thio-DAP (1) had a ZOI of 22.67 ± 0.58, while ciprofloxacin had a ZOI of 23.67 ± 0.58. To synthesize thio-DAP (1) and oxa-DAP (2), l-cysteine was used as a precursor for the L-stereocenter (l-cysteine), which is recognized by the dapF enzyme's active site and selectively binds to the ligand's L-stereocenter. Docking studies of these compounds were carried out using the programme version 11.5 Schrodinger to reveal the hydrophobic and hydrophilic properties of these complexes. The docking scores of compounds one and two were −9.823 and −10.098 kcal/mol, respectively, as compared with LL-DAP (−9.426 kcal/mol.). This suggests that compounds one and two interact more precisely with dapF than LL-DAP. Chemicals one and two were synthesized via the SBDD (structure-based drug design) approach and these act as inhibitors of the dapF in the lysine pathway of bacterial cell wall synthesis. [ABSTRACT FROM AUTHOR]

Formulation and characterization of Luliconazole (LZL) nanosuspensions using modified starch ester polymer to increase solubility. X-ray analysis of A6 and B4 lyophilized nanosuspensions confirmed amorphous nature having % relative crytalinilty of 48.453, 41.374% and crystallite size of 21 and 35 nm; respectively. However, solubility of lyophilized nanosuspension improved by more than 370 fold in comparison to that of pure LZL-API which brings it in soluble form at pH-1.2. In-vitro antifungal studies revealed that lyophilized nanosuspension enhanced activity against fungi yeasts (Candida albican, Candida auris) and Aspergillus (A. Flavus, A. Nigar) when compared to LZL marketed cream. [ABSTRACT FROM AUTHOR]

It is a known fact that HIV infection remains a serious public health problem throughout the world, and the need to constantly develop new antiretroviral drugs to combat HIV emerges from the fact that repetitive mutations occurring in viral enzymes make this virus resistant to antiretroviral drugs. This resistance causes failure of treatment, and hence, for many years, extensive research has been to discover newer possibilities for fighting this disease at a molecular level, along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped, and in the process, many heterocyclic scaffolds have been used to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating different types of viral infections. This concise and rigorous literature explains the journey and highlights the various strategies to develop new anti-HIV drug candidates., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We created thiazole and oxazole analogues of diaminopimelic acid (DAP) by replacing its carboxyl groups and substituting sulphur for the central carbon atom. Toxicity, ADME, molecular docking, and in vitro antimicrobial studies of the synthesized compounds were carried out. These compounds displayed significant antibacterial efficacy, with MICs of 70-80 µg/mL against all tested bacteria. Comparative values of the MIC, MBC, and ZOI of the synthesized compound were noticed when compared with ciprofloxacin. At 200 µg/mL, thio-DAP (1) had a ZOI of 22.67 ± 0.58, while ciprofloxacin had a ZOI of 23.67 ± 0.58. To synthesize thio-DAP (1) and oxa-DAP (2), l-cysteine was used as a precursor for the L-stereocenter (l-cysteine), which is recognized by the dap F enzyme's active site and selectively binds to the ligand's L-stereocenter. Docking studies of these compounds were carried out using the programme version 11.5 Schrodinger to reveal the hydrophobic and hydrophilic properties of these complexes. The docking scores of compounds one and two were -9.823 and -10.098 kcal/mol, respectively, as compared with LL-DAP (-9.426 kcal/mol.). This suggests that compounds one and two interact more precisely with dap F than LL-DAP. Chemicals one and two were synthesized via the SBDD (structure-based drug design) approach and these act as inhibitors of the dap F in the lysine pathway of bacterial cell wall synthesis.

Background: Currently used anti-inflammatory drugs are associated with some severe side effects such as gastric irritation, which may range from simple discomfort to ulcer formation. Therefore, the development of potent anti-inflammatory drugs with fewer side effects is important. Benzimidazole, tetrazole and its various derivatives have been used in the synthesis of numerous heterocyclic compounds. In the past few decades, these compounds received much attention due to their diverse array of biological activities. As these heterocycles are known to possess anti-inflammatory activity individually, we thought it worthwhile to link these heterocycles, synthesize them and evaluate for possible changes in this anti-inflammatory activity., Methods: Novel benzimidazole linked tetrazole compound 2-{[2-(1H-tetrazole-5-yl)ethyl] sulfanyl}-1,3-benzimidazole (3) was synthesized by cyclization of 3-(1,3-benzimidazol-2-ylsulfanyl) propanenitrile in presence of sodium azide. A series of tetrazolobenzimidazole derivatives (3a-h) were synthesized by the reaction of compound (3) with acid chlorides. All the synthesized compounds were subjected to structural elucidation by IR, 1H-NMR spectroscopy, Mass spectrometry and elemental analyses. The newly synthesized compounds were screened for anti-inflammatory activity by carrageenan-induced paw oedema method in albino rats., Results: Compounds (3a, 3c, 3g) which contain acetyl, benzoyl and benzoyl moieties; respectively at N-1of tetrazole exhibited anti-inflammatory activities comparable with standard drug diclofenac. Other compounds exhibited anti-inflammatory activity less than the standard. The differences between control and treatment group were tested using one way ANOVA followed by Dunnett's test. A probability value less than 0.01 was considered to be statistically significant. The GraphPad Instat 3.0 version was used for statistical analysis., Conclusion: Synthesized compounds having anti-inflammatory activity better than standard were found to be 1-{5-[2-(benzimidazol-2-yl-sulfanyl)ethyl]-2H-tetrazol-2yl}methanone (3c) and 1-{5-[5-methoxy-2-(benzimidazol-2-yl-sulfanyl)ethyl]-2H-tetrazol-2yl}methanone (3g) and the compounds (3a, 3e, 3f) were found to exhibit anti-inflammatory activity comparable to that of standard. All the compounds were found to cause less gastric ulceration than the standard drug diclofenac.