Highlights: CPL-AgNPs exhibited improved biomimetic attributes. Antibiotic resistance against pathogens were challenged through use of CPL-AgNPs. Supercapacitor application of facile synthesized AgNPs for the first time demonstrated improved physical application.

New Delhi metallo-β-lactamase-1 (NDM-1), expressed in different Gram-negative bacteria, is a versatile enzyme capable of hydrolyzing β-lactam rings containing antibiotics such as penicillins, cephalosporins, and even carbapenems. Multidrug resistance in bacteria mediated by NDM-1 is an emerging threat to the public health, with an enormous economic burden. There is a scarcity in the availability of specific NDM-1 inhibitors, and also a lag in the development of new inhibitors in pharmaceutical industries. In order to identify novel inhibitors of NDM-1, we screened a library of more than 20 million compounds, available at the MCULE purchasable database. Virtual screening led to the identification of six potential inhibitors, namely, MCULE-1996250788-0-2, MCULE-8777613195-0-12, MCULE-2896881895-0-14, MCULE-5843881524-0-3, MCULE-4937132985-0-1, and MCULE-7157846117-0-1. Furthermore, analyses by molecular docking and ADME properties showed that MCULE-8777613195-0-12 was the most suitable inhibitor against NDM-1. An analysis of the binding pose revealed that MCULE-8777613195-0-12 formed four hydrogen bonds with the catalytic residues of NDM-1 (His120, His122, His189, and Cys208) and interacted with other key residues. Molecular dynamics simulation and principal component analysis confirmed the stability of the NDM-1 and MCULE-8777613195-0-12 complex. The in vitro enzyme kinetics showed that the catalytic efficiency (i.e., k_cat/K_m) of NDM-1 on various antibiotics decreased significantly in the presence of MCULE-8777613195-0-12, due to poor catalytic proficiency (k_cat) and affinity (K_m). The IC₅₀ value of MCULE-8777613195-0-12 (54.2 µM) was comparable to that of a known inhibitor, i.e., D-captopril (10.3 µM). In sum, MCULE-8777613195-0-12 may serve as a scaffold to further design/develop more potent inhibitors of NDM-1 and other β-lactamases.

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method.

A rapid, synchronized liquid chromatographic method was established for the estimation of hydrochlorothiazide (HCZ), amlodipine (AMD), olmesartan (OLM), telmisartan (TEL), and irbesartan (IRB) in binary and ternary coformulations using the same chromatographic conditions. Five analytes were separated on a Zorbax C18 column using isocratic elution with a mobile phase consisting of acetonitrile, methanol, and 20 mM phosphate buffer (pH 3.5) in a ratio of 45:20:35% v/v. The analytes were detected at a wavelength of 230 nm at ambient temperature. Furthermore, the proposed liquid chromatographic procedure was validated for linearity, precision, accuracy, stability, and robustness using an experimental design. Analytes were separated with good resolution within 3.5 min. Analytes showed good linearity in a concentration satisfactory to analyze the different ratios of these analytes in the formulations. Pareto charts showed that the flow rate and mobile phase composition have a significant effect on the peak area of analytes and hence need to be carefully controlled, however, the method is robust. Finally, the different formulations consisting of HCZ, AMD, OLM, TEL, and IRB in different ratios were analyzed with high accuracy using an optimized HPLC method and compared with reported methods. Furthermore, the reported HPLC procedure is simple, rapid, and accurate and therefore can used for regular quality control of binary and ternary formulations using the same stationary and mobile phase.