The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption.

Background: Chemical hazard is one of the most prominent side effects that come out along with the benefits of pharmaceutical production. Chemicals usage and waste production are involved in each step of production and are found to be in high percentage at the stage of quality testing. Conventional quality testing (assay) involves the use of solvents and reagents that generates high flammable and non-flammable waste and also enhanced the per batch cost of the medicine, whereas green chemistry offers a benign environment for drug designing, manufacturing, and analysis. Results: In the present study, a green FTIR method for assay of antiviral drugs entecavir is developed and validated as per ICH Q2_R1 guidelines. A calibration curve is plotted between absorbance and concentration, yielding excellent linearity with a correlation coefficient (r²) value of 0.9991 in the concentration range of 0.25–0.75 mg. Conclusion: The developed method was validated and was very specific, accurate (99.9–100%) at three levels of 80, 100, and 120% of test concentration and precise with < 1% RSD. The LOD of the method is 0.0674 mg and is able to quantify the active at the limit of 0.2042 mg. Four different drug brands available in the local market are assayed by the validated method, and %recoveries are found to be in the range of 99–101%. Graphical Green Chemistry Approach: Method Development and Validation for Identification and Quantification of Entecavir using FT-IR in Bulk and Pharmaceutical Dosage Form

A series of synthesized imine derivatives (3a–m), including thio-semicarbazone, semicarbazone, thiazole and oxazole functional moieties, were examined for in vitro urease inhibition activity.