Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (112) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, ¹H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC=0.8g/mL) and 8 (MIC=0.8g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of 7.36 and 7.17kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

Tuberculosis, colloquially referred to as TB, is a highly prevalent bacterial infection that persists as a substantial global health concern. The present article centers its attention on the comprehensive exploration of the synthesis, molecular docking, and molecular dynamic simulation investigations pertaining to substituted benzimidazole derivatives. Additionally, a meticulous assessment of their anti-TB activities is conducted. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FT-IR, 1H-NMR, and Mass spectra. The Microplate Alamar Blue Assay (MABA) was used to evaluate the anti-mycobacterial activity of synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/ml) and 8 (MIC = 0.8 g/ml) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard (Isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of -7.36 and − 7.17 kcal/mol, respectively. Both substances were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

INTRODUCTION Fast disintegrating/dissolving medicine delivery devices are oral films that swiftly disintegrate or adhere in the mouth. It includes the ability to administer systemic medications without having any first-pass effects. A first-generation antihistamine from the phenothiazine family is promethazine HCl. It is effective in treating motion sickness but it has a poor oral bioavailability. The study aims is to formulate promethazine fast dissolving oral film using natural and synthetic polymers and compare the formulations. MATERIAL AND METHODS This experimental study was conducted in the Pharmaceutic laboratory of Department of Pharmacy at Universal College of Medical Sciences, Bhairahawa, Nepal from February 2022 to July 2022. Fast dissolving oral films of promethazine were prepared by solvent casting method using polymers and plasticizers in varying concentrations. Weight variation, thickness variation, surface pH, folding endurance, swelling index, disintegration duration, dissolution study and medication content were among the several in vitro assessment criteria that were identified. RESULTS When examined for physical characteristics, thickness, weight uniformity, in vitro disintegration time, folding durability, drug content, and an in vitro drug release, films were determined to be adequate. The films of the F2 formulation demonstrated an increased rate of drug dissolution with a drug content of 99.17%, a disintegration time of 38 sec, and a drug release of more than 99% within 16 min. CONCLUSION Synthetic polymer (Hydroxypropyl methyl cellulose) showed better result in comparison to natural polymer (Sodium alginate).

Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cheap, effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent present in leaves extract and evaluate the alpha-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. The extraction of Adhatoda vasica leaves was performed with ethanol using the Soxhlet apparatus. Then the phytochemical screening of ethanolic extract was performed. Different concentration (0.1mg/ml to 1mg/ml) of ethanolic extract of leaves, acarbose, sitagliptin, and metformin was prepared and all concentrations were evaluated for alpha-amylase inhibitory activity through the spectrophotometric method. The percentage yield of ethanolic extract was found to be 6.69%. Maximum inhibition of alpha amylase was shown by acarbose at a concentration of 1mg/ml and found to be 74.879±0.0056 whereas, plant extract at a concentration of 1mg/ml showed inhibition of alpha-amylase was 56.763±0.0035. Percentage of alpha-amylase activity by plant extract was found to be dose-dependent. It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer drugs with lesser side effects.