Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases.

Considering the importance of acetylcholine esterase (AChE, BchE) and α-glucosidase in the treatment of Alzheimer's disease and diabetes mellitus, the synthesis of novel azinane triazole-based derivatives as effective acetylcholinesterase (AchE), α-glucosidase, urease, lipoxygenase (LOX), and butyrylcholinesterase (BChE) inhibitors is described. Azinane analogue (2) was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4H-1,2,4-triazol-5-yl) piperidine (8) through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine (3), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine (5), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine (7). The target molecules, 1-(4-toluenesulfonyl)-4-[3-(N-alkyl/phenyl/aryl-2-ethanamoyl thio)-4-methyl-4H-1,2,4-triazol-5-yl] piperidine (12a-o), were achieved through the reaction of 8 with N-alkyl/phenyl/aryl-2-bromo ethanamides (11a-o) as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines (9a-o) and 2-bromo ethanoyl bromide (10). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives 12d and 12m with IC₅₀ = 0.73 ± 0.54; 36.74 ± 1.24; 19.35 ± 1.28; 0.017 ± 0.53; and 0.038 ± 0.50 μM are found to be the most potent AChE, α-glucosidase, urease, and BChE inhibitors. The high inhibition potential of synthesized molecules against AChE, α-glucosidase, urease, and BChEenzymes inferred their role in enzyme inhibition properties.

Alcalase was immobilized on glyoxyl 4% CL agarose beads. This permitted to have Alcalase preparations with 50% activity retention versus Boc-l-alanine 4-nitrophenyl ester. However, the recovered activity versus casein was under 20% at 50 °C, as it may be expected from the most likely area of the protein involved in the immobilization. The situation was different at 60 °C, where the activities of immobilized and free enzyme became similar. The chemical amination of the immobilized enzyme or the treatment of the enzyme with glutaraldehyde did not produce any significant stabilization (a factor of 2) with high costs in terms of activity. However, the modification with glutaraldehyde of the previously aminated enzyme permitted to give a jump in Alcalase stability (e.g., with most than 80% of enzyme activity retention for the modified enzyme and less than 30% for the just immobilized enzyme in stress inactivation at pH 7 or 9). This preparation could be used in the hydrolysis of casein at pH 9 even at 67 °C, retaining around 50% of the activity after 5 hydrolytic cycles when the just immobilized preparation was almost inactive after 3 cycles. The modified enzyme can be reused in hydrolysis of casein at 45 °C and pH 9 for 6 cycles (6 h) without any decrease in enzyme activity.