iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation

Inducible nitric oxide synthase (iNOS) plays an important role in the inflammatory processes via accelerating the production of nitric oxide (NO). The efforts to develop small molecules as selective inhibitors of iNOS are being reported across the globe. The current study explores varied benzimidazole-coumarin derivatives as anti-iNOS agents. Literature survey suggests 2-aminobenzimidazole, coumarin nucleus, and 4-atom linker as important structural components for iNOS inhibition. Target compounds were designed and synthesized by coupling 2-aminobenzimidazole with (un)substituted coumarin through different linkers. These were docked in iNOS (1QW4) and nNOS (1QW6) targets to ascertain their iNOS selectivity, and evaluated for NO and iNOS inhibitory activities in vitro. The most active inhibitors were subsequently evaluated for acute toxicity and anti-inflammatory activity using carrageenan-induced rat paw edema model in vivo. All compounds possessed moderate to good NO and iNOS inhibitory activities. Compounds 14a, 14b, 14d, and 14e were the most potent inhibitors in vitro. These were found to significantly reduce the inflammation. Compounds 14d and 14e have been identified as the most potent iNOS inhibitors to combat inflammation. These derivatives may serve as potential compounds as such against iNOS, or as leads for the development of novel anti-iNOS agents

Novel coumarin–benzimidazole derivatives as antioxidants and safer anti-inflammatory agents

Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles, novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position. The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile. Two series of coumarin–benzimidazole derivatives (4a–e and 5a–e) were synthesized and evaluated for anti-inflammatory activity and antioxidant activity. Compounds 4c, 4d and 5a displayed good anti-inflammatory (45.45%, 46.75% and 42.85% inhibition, respectively, versus 54.54% inhibition by indomethacin) and antioxidant (IC50 of 19.7, 13.9 and 1.2 µmol/L, respectively, versus 23.4 µmol/L for butylatedhydroxytoluene) activities. Evaluation of ulcer index and in vivo biochemical estimations for oxidative stress revealed that compounds 4d and 5a remain safe on gastric mucosa and did not induce oxidative stress in tissues. Calculation of various molecular properties suggests the compounds to be sufficiently bioavailable

High temperature oxidation behaviour of NiCrAlY clad developed on SS-304 through microwave irradiation

The current study investigates the underlying causes of the microstructural features, microhardness and high-temperature oxidation behaviour of the NiCrAlY powder cladded stainless steel (SS-304) substrate. The cladding was performed by utilizing an industrial multimode microwave apparatus, operating at 1.1 kW and 2.45 GHz with a 900 s processing time. The fabricated clad layer unveiled perfect metallurgical integration with the substrate and was noticed to be free from obvious flaws, including cracks or improper bonding at the clad-base material interface. The deposited clad layer revealed an equiaxed dendritic microstructure at the top while a typical columnar dendritic microstructure at the centre. The X-ray diffraction (XRD) examination of the clad sample revealed the existence of intermetallic compounds like γ′-Ni3Al, and Al5Y3O12 in addition to a solid solution of Iron (Fe) and Nickel (Ni) and chromium (Cr) enriched matrix. The microhardness of the clad layer was noticed to be higher than that of the uncladded SS-304 specimen. High-temperature oxidation investigation performed at 900 °C in air revealed weight gain by all the samples (bare and clad) in a parabolic fashion, initially for around 10 cycles of oxidation, beyond which the weight gain is noticed to saturate. The maximum oxidation resistance exhibited by the clad sample was credited with having intensified α-Al2O3 in the surface layer