Synthesis, biological evaluation, and molecular docking study of chromen-linked hydrazine carbothioamides as potent α-glucosidase inhibitors.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Several novel chromen-linked hydrazine carbothioamide (3a-r) were designed and synthesized by condensation of chromone-3-carbaldehyde with a variety of substituted thiosemicarbazides. The structures of these new analogues were elucidated through various advanced spectroscopic techniques (1 H NMR, 13 C NMR, and ESI-MS). The resulted compounds were screened for α-glucosidase inhibitory potential and all the compounds (3a-r) exhibited potent inhibition of α-glucosidase with IC50 values ranging 0.29-53.70 µM. Among them compounds 3c, 3f, 3h, and 3r displayed the highest α-glucosidase inhibitor capability with IC50 values of 1.50, 1.28, 1.08, and 0.29 µM, respectively. Structure-activity relationship showed that different substituted groups are responsible for the variation in the α-glucosidase inhibition. The kinetics studies of the most active inhibitor (3r) were performed, to investigate the mode of inhibition and dissociation constants (Ki), that indicated a competitive inhibitor with Ki value of 1.47 ± 0.31 µM. Furthermore, molecular docking studies was performed to reveal the possible interactions, such as H-bonding, or π-π stacking, with the key residues of α-glucosidase. Docking analysis revealed the importance of hydrazine carbothioamide moiety of compounds in the attachment of ligands with the crucial residues of α-glucosidase. The estimated pharmacokinetic, physicochemical, and drug likeness properties of compounds 3a-r reflects that these molecules have acceptable range of these properties.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 µM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.

Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 µM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Novel Polyhydroquinoline-Hydrazide-Linked Schiff's Base Derivatives: Multistep Synthesis, Antimicrobial, and Calcium-Channel-Blocking Activities.

Polyhydroquinoline (PHQ) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, twenty-five (3-27) new Schiff's base derivatives of polyhydroquinoline hydrazide were synthesized in excellent to good yields by a multi-component reaction. The structures of the synthesized products (1-27) were deduced with the help of spectroscopic techniques, such as 1H-, 13C -NMR, and HR-ESI-MS. The synthesized products (1-27) were tested for their antibacterial and in vitro calcium -channel-blocking (CCB) potentials using the agar-well diffusion method, and isolated rat aortic ring preparations, respectively. Among the series, sixteen compounds were found to inhibit the growth of Escherichia coli and Enterococcus faecalis. Among them, compound 17 was observed to be the most potent one at a dose 2 µg/mL, with an 18 mm zone of inhibition against both bacteria when it was compared with the standard drug amoxicillin. Eight compounds showed CCB activity of variable potency; in particular, compound 27 was more potent, with an EC50 value of 0.7 (0.3-1.1) µg/mL, indicating their CCB effect.

Assessment of heavy metal and petroleum hydrocarbon contamination in the Sultanate of Oman with emphasis on harbours, marinas, terminals and ports.

The assessment here includes data on levels of contaminants (petroleum hydrocarbons and heavy metals) in sediments and biomonitor organisms, including the eulittoral rock oyster Saccostrea cucullata and subtidal biomonitors, the barnacle Balanus trigonus and the antipatharian coral Antipathes sp., at harbours, marinas, terminals and large ports along the coastline of Oman. TBT levels in harbour and port sediments up to a maximum of 100ppb TBT dry weight are highlighted. Oysters contained concentrations up to 367ppm mg TPH/kg dry weight. The maximum levels of Cd, Cu, Pb and Zn were found in the subtidal sediments and barnacles at the oil tanker loading Single Buoy Mooring stations in Mina Al Fahal. In general, the levels of most of the contaminants analysed are at low to moderate concentrations compared to those in highly contaminated sites such as shipyards and dry docks, but continued monitoring is recommended especially during any dredging campaigns.