LC-MS profiling, in vitro and in silico C-ABL kinase inhibitory approach to identify potential anticancer agents from Dalbergia sissoo leaves.

Belonging to the Fabaceae family, Dalbergia sissoo, a versatile plant, has gained prominence for its potent medicinal attributes, especially antipyretic, anti-inflammatory, and cardioprotective properties, as well as the use of its leaf juice in cancer treatment. Despite these recognized applications by natives and tribals, comprehensive insight into its biological activities and chemical composition remains limited. This study aimed to explore the cytotoxic potential of sequentially extracted leaf extracts from Dalbergia sissoo using various solvents, aiming to unveil the array of phytochemicals through LC-MS profiling. Among the extracts evaluated, the extract employing methanol:water extracting media (HN-2) appeared with the most remarkable results in both phytochemical diversity and biological activity. Furthermore, in vitro results of HN-2's in vitro anticancer efficacy were confirmed through in silico molecular docking and molecular dynamics simulation. These analyses demonstrated its ability to inhibit C-ABL kinase within leukemia K562 cells, directing that Dalbergia sissoo leaves serve as a bioactive agent reservoir. Consequently, this suggests that the Dalbergia sissoo plant is a potential source of bioactive compounds that can be used as a precursor for developing new cancer inhibitors, mainly targeting leukemia.

α-Amylase and mycobacterium-TB H37Rv antagonistic efficacy of novel pyrazole-coumarin hybrids: an in vitro and in silico investigation.

The present investigation of minutiae to acquire structural information of the novel pyrazole-coumarin hybrids (PC1-PC10) synthesized using ultrasound methods and characterized using different spectroscopic techniques: mass, 1H-NMR, 13 C-NMR and IR spectroscopy, and theoretically explored using the DFT approach with a B3LYP/6-311G (d, p) basis set, and there in vitro, antagonistic efficacy against α-amylase and mycobacterium-TB H37Rv are described in this article. Pyrazole-coumarin hybrids (PC1-PC10) showed α-amylase inhibition ranging from IC50 (0.32-0.58 mM) when compared with acarbose (IC50 = 0.34 mM). Similarly, Mycobacterium-TB H37Rv strain inhibition screening showed MIC values ranging from 62.5 to 1000 µg/mL when compared with rifampicin and isoniazid MIC = 0.25 and 0.20 µg/mL, respectively. Molecular docking and MD simulation studies were performed to determine the active sites and rationalize the activities of the active compounds. To investigate the binding conformation and dynamics responsible for their activity, the three most active compounds (PC1, PC3 and PC6) were docked into the porcine pancreatic α-amylase active site (PDB ID:1OSE), and mycobacterium-TB H37Rv active site (PDB ID: 4TZK). The binding interactions between PC1, PC3, and PC6 with α-amylase were like those responsible for inhibiting α-amylase by acarbose. Also, the mycobacterium-TB H37Rv inhibiting responsible residues were compared with standard isoniazid and rifampicin.Communicated by Ramaswamy H. Sarma.

Dalbergia sissoo phytochemicals as EGFR inhibitors: an in vitro and in silico approach.

The safest and most effective sources of medications are natural and traditional medicines derived from plants and herbs. In Western India, various parts of the Dalbergia sissoo plant, which belongs to the Fabaceae family, have been traditionally used to treat different types of cancer by the local tribes. However, this claim has not been scientifically proven yet. Thus, the purpose of this study was to examine the antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity) and anticancer effects of different plant extracts from Dalbergia sissoo bark, root, and branch on six different cancer cell lines (K562, PC3, A431, A549, NCIH 460, and HEK 293 T) using in vitro cell viability and cytotoxicity assays. The study also involved in silico docking, MD simulation, and ADME studies of previously reported bioactive compounds from the same parts of the plant to confirm their bioactivity. The DPPH radical scavenging experiment findings showed that the methanol: water extract of the bark had a more significant antioxidant activity IC50 (45.63 ± 1.24 mg/mL). Furthermore, the extract prevented the growth of the A431, A549, and NCIH 460 cancer cell lines with the lowest IC50 values of 15.37, 29.09, and 17.02 g/mL, respectively, demonstrating remarkable anticancer potential. Molecular docking and dynamic simulation studies revealed that Prunetin, Tectorigenin, and Prunetin 4'-O-Galactoside show efficient binding to the EGFR binding domain. This study suggests that tested hits may have antioxidant and anticancer agents and can be considered for future applications in the pharma sector.Communicated by Ramaswamy H. Sarma.

Design and synthesis of pyrrolo[2,3-d]pyrimidine linked hybrids as α-amylase inhibitors: molecular docking, MD simulation, ADMET and antidiabetic screening.

Novel pyrrolo[2,3-d]pyrimidine-based analogues were designed, synthesized, and evaluated for their ability to inhibit the α-amylase enzyme in order to treat diabetes. In vitro antidiabetic analysis demonstrated excellent antidiabetic action for compounds 5b, 6c, 7a, and 7b, with IC50 values in the 0.252-0.281 mM range. At a 200 µg/mL concentration, the exceptional percent inhibition values for compounds 5a, 5b, 5d, and 6a varied from 97.79 ± 2.86% to 85.56 ± 4.13% overperforming the standard (acarbose). Molecular docking of all compounds performed with Bacillus paralicheniformis α-amylase enzyme. The most active compounds via in vitro and non-toxic via in silico ADMET and molecular docking analysis, hybrids 6c, 7a, and 7b displayed binding affinity from - 8.2 and - 8.5 kcal/mol. Molecular dynamic simulations of most active compound 5b and 7a investigated into the active sites of the Bacillus paralicheniformis α-amylase enzyme for a 100-ns indicating the stability of hybrid-protein complex. Consistent RGyr values for the two complexes under study further suggest that the system's proteins are closely packed in the dynamic state. Synthesized analogs' in vitro biological assessments, ADMET, molecular docking, and MD modelling reveal that 5b, 6c, 7a, and 7b hybrid analogs may be employed in the development of future antidiabetic drugs.

The Inhibition of Mild Steel Corrosion in 1 N HCl by Imidazole Derivatives.

The inhibition effect of imidazole derivatives 4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid (MPBI) and 1,4'-Dimethyl-2'-propyl-1H,3'H-2,5'-dibenzimidazole (DPBI) against mild steel corrosion in 1 N HCl solutions were evaluated using conventional weight loss, potentiodynamic polarization, linear polarization and electrochemical impedance spectroscopy. The weight loss results showed that both are excellent corrosion inhibitors, electrochemical polarizations data revealed the mixed mode of inhibition and the results of electrochemical impedance spectroscopy have shown that the change in the impedance parameters, charge transfer resistance and double layer capacitance, with the change in concentration of the inhibitor is due to the adsorption of the molecule leading to the formation of a protective layer on the surface of mild steel. The inhibition action of these compounds was, assumed to occur via adsorption on the steel surface through the active centres contained of the molecule.