Inhibitor

Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of evolutionarily conserved intracellular protein deacetylases that can catalyze the acetyl group removal from the specific Nε-acetyl-lysine (AcK) side chains on a variety of proteins from all kingdoms of life. Yeast Sir2 was the first sirtuin identified, and so far seven sirtuins (i.e. SIRT1-7) have been found in mammals including humans. The sirtuin-catalyzed deacetylation reaction has captured tremendous interest during the past a few years because of (i) its increasingly demonstrated importance in many crucial biological processes such as gene transcription, metabolism, and aging, and thus its therapeutic potential for metabolic and age-related diseases and cancer, and (ii) its unique deacetylation chemistry. Specifically, the sirtuin-catalyzed AcK side chain deacetylation is not merely an amide hydrolysis reaction, instead is coupled to the nicotinamide cleavage from β- nicotinamide adenine dinucleotide (β-NAD+ or NAD+) with the generation of three enzymatic products, i.e. the deacetylated protein species, nicotinamide, and 2’-O-acetyl-ADP-ribose (2’-O-AADPR). Here the author would like to review the past endeavors on developing mechanism-based sirtuin modulators (inhibitors and activators). The first part of this article will provide an updated mechanistic picture of the sirtuin-catalyzed deacetylation reaction. The second part will be focused on how the mechanistic knowledge has been exploited for the design of effective sirtuin modulators.

Dopamine -monooxygenase (DBM) catalyses the conversion of dopamine to norepinephrine in the catecholamine biosynthetic pathway. The substrate specificity of DBM is wide and the enzyme is capable of performing a variety of oxidations. While the crystal structure of DBM is not yet available, various indirect data allows insight into the enzyme’s machinery. Considered an attractive therapeutic target for the treatment of hypertension and congestive heart failure, DBM and its inhibitors have received attention by medicinal chemists over the last four decades. Although several QSAR models for DBM inhibitors have been generated, these models are actually unable to explain the exceptionally high potency of the latest generation of inhibitors.

Ribosomal S6 kinase (RSK) is a family of serine/threonine kinases that has been identified as a promising anti-cancer target. While a number of protein kinase inhibitors that have potent activity against other serine/threonine kinases were shown to also inactivate RSK, there is keen interest in the three different inhibitor chemotypes that were shown to be RSK specific, since these compounds have tremendous utility as chemical probes in elucidating the biochemistry of the RSK signaling cascade and unraveling the molecular basis of cancer. Because each compound may have therapeutic potential, the nonspecific kinase inhibitors as well as the RSK specific inhibitors will be discussed.

Corrosion of mild steel in HCl was investigated using the weight loss method. The mild steel used was cut into 16 coupons with 5.0 cm x 5.0 cm x 0.2 cm dimensions which were degreased with ethanol and washed with distilled water and finally weighed. The mild steel coupons were exposed to HCl with varied concentrations (0, 10, 25 and 40%) of Garcinia kola extracts used as corrosion inhibitors for 4 hours at 400C and 600C respectively. The result showed that at 400C; the inhibition efficiency of 65.5% was observed at 25 % HCl concentration and 62.9% at 40% HCl concentration while at 600C; inhibition efficiency of 87.7% was at 25% HCl concentration and 88.1% at 40% concentration respectively. It can be concluded that increase in concentration increases the inhibition efficiency. The presence of flavonoid and alkanoids in bitter kola stem is a good inhibitor.

The addition of inhibitors is a standard practice in industries to control corrosion.
However, no research had been done on the use of Almond fruits e
corrosion inhibitor.This study investigated the optimisation of Almond leaves extract
as corrosion inhibitor on Alu
inhibitor concentration (0.2 g/l
investigated using Response Surface Methodology (RSM). The results revealed that
Almond leaves extract effectively
the acidc medium. The concentration of 0.38 g/l, t
gave the optimum conditions to validate the predicted v
of 97.9% agreed closely with that obtained from the predicted model. This study
revealed that Almond fruit extract could be recommedned as a low cost and a good
inhibitor for acid corrosion of Aluminum

Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in
various cellular functions, such as telomere homeostasis, Wnt/-catenin signaling, glucose metabolism, and cell cycle progression. In these processes, Tankyrases regulate the interactions and stability of target proteins by poly (ADP-ribosyl)ation. Modified proteins are subsequently recognized by the E3 ubiquitin ligase RNF146, poly-ubiquitinated and predominantly guided to 26S proteasomal degradation.
Several small molecule inhibitors have been described for Tankyrases; they compete with the co-substrate NAD+ for binding to the ARTD catalytic domain. The recent, highly potent and selective inhibitors possess several properties of lead compounds and can be used for proof-of-concept studies in cancer and other Tankyrase linked diseases.