In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides.

Series of the 6-bromo/iodo substituted 2-aryl-4-methyl-1,2-dihydroquinazoline-3-oxides and their mixed 6,8-dihalogenated (Br/I and I/Br) derivatives were evaluated for inhibitory properties against α-glucosidase and/or α-amylase activities and for cytotoxicity against breast (MCF-7) and lung (A549) cancer cell lines. The 6-bromo-2-phenyl substituted 3a and its corresponding 6-bromo-8-iodo-2-phenyl-substituted derivative 3i exhibited dual activity against α-glucosidase (IC50 = 1.08 ± 0.02 µM and 1.01 ± 0.05 µM, respectively) and α-amylase (IC50 = 5.33 ± 0.01 µM and 1.18 ± 0.06 µM, respectively) compared to acarbose (IC50 = 4.40 ± 0.05 µM and 2.92 ± 0.02 µM, respectively). The 6-iodo-2-(4-fluorophenyl)-substituted derivative 3f, on the other hand, exhibited strong activity against α-amylase and significant inhibitory effect against α-glucosidase with IC50 values of 0.64 ± 0.01 µM and 9.27 ± 0.02 µM, respectively. Compounds 3c, 3l and 3p exhibited the highest activity against α-glucosidase with IC50 values of 1.04 ± 0.03, 0.92 ± 0.01 and 0.78 ± 0.05 µM, respectively. Moderate cytotoxicity against the MCF-7 and A549 cell lines was observed for these compounds compared to the anticancer drugs doxorubicin (IC50 = 0.25 ± 0.05 µM and 0.36 ± 0.07 µM, respectively) and gefitinib (IC50 = 0.19 ± 0.04 µM and 0.25 ± 0.03 µM, respectively), and their IC50 values are in the range of 10.38 ± 0.08-25.48 ± 0.08 µM and 11.39 ± 0.12-20.00 ± 0.05 µM, respectively. The test compounds generally exhibited moderate to strong antioxidant capabilities, as demonstrated via robust free radical scavenging activity assays, viz., DPPH and NO. The potential of selected derivatives to inhibit superoxide dismutase (SOD) was also investigated via enzymatic assay in vitro. Molecular docking revealed the N-O moiety as essential to facilitate electrostatic interactions of the test compounds with the protein residues in the active site of α-glucosidase and α-amylase. The presence of bromine and/or iodine atoms resulted in increased hydrophobic (alkyl and/or π-alkyl) interactions and therefore increased inhibitory effect against both enzymes.

Biological evaluation the 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones as potential dual α-glucosidase and α-amylase inhibitors with antioxidant properties.

The 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones (azaborininone) were synthesized as analogues of the 2-arylquinazoline-4-ones and screened through enzymatic assay in vitro for inhibitory effect against α-glucosidase and α-amylase activities. These azaborininones exhibited moderate to good inhibitory effect against these enzymes compared to acarbose used as a reference standard. The results are supported by the enzyme-ligand interactions through kinetics (in vitro) and molecular docking (in silico) studies. The test compounds also exhibited significant antioxidant activity through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. These azaborininone derivatives exhibited no effect on the viability of the human lung cancer (A549) cell line after 24 hr and were also not toxic towards the Vero cells.

Synthesis, α-glucosidase inhibition and antioxidant activity of the 7-carbo-substituted 5-bromo-3-methylindazoles.

Series of 7-aryl- (3a-f), 7-arylvinyl- (3g-k) and 7-(arylethynyl)-5-bromo-3-methylindazoles (4a-f) have been evaluated through enzymatic assay in vitro for inhibitory effect against α-glucosidase activity and for antioxidant potential through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 3a-k and 4a-f showed significant to moderate α-glucosidase inhibition with IC50 values in the range of 0.50-51.51 µM and 0.42-23.71 µM compared with acarbose drug (IC50 = 0.82 µM), respectively. 5-Bromo-3-methyl-7-phenyl-1H-indazole (3a), 5-bromo-3-methyl-7-styryl-1H-indazole (3h) and 5-bromo-3-methyl-7-styryl-1H-indazole (4a) exhibited moderate to significant antigrowth effect against the breast MCF-7 cancer cell line and reduced cytotoxicity against the human embryonic kidney derived Hek293-T cells when compared to doxorubicin as reference standard. Non-covalent (alkyl, π-alkyl and π-π T shaped), electrostatic (π-sulfur and/or π-anion) and hydrogen bonding interactions are predicted to increase interactions with protein residues, thereby enhancing the inhibitory effect of these compounds against α-glucosidase.

The Occurrence and Diversity of Waterborne Fungi in African Aquatic Systems: Their Impact on Water Quality and Human Health.

Currently, there is a worldwide growing interest in the occurrence and diversity of fungi and their secondary metabolites in aquatic systems, especially concerning their role in water quality and human health. However, this concern is hampered by the scant information that is available in the literature about aquatic fungi and how they affect water quality. There are only few published reports that link certain species of aquatic fungi to human health. The common aquatic fungal species that have been reported so far in African aquatic systems belong to the hyphomycetes kingdom. This paper thus aims to survey the information about the occurrence and factors that control the distribution of different species of fungi in African aquatic systems, as well as their effect on water quality and the possible metabolic pathways that lead to the formation of toxic secondary metabolites that are responsible for the deterioration of water quality. This review will also investigate the analytical and bioanalytical procedures that have been reported for the identification of different species of waterborne fungi and their secondary metabolites.