Inhibitor

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.

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.

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.

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.

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.

There is an urgent need to develop novel anti-malarials in view of the increasing disease burden and growing resistance of the currently used drugs against the malarial parasites. Proliferation inhibitors targeting P. falciparum intraerythrocytic cycle are one of the important classes of compounds being explored for its potential to be novel antimalarials. Support Vector Machine (SVM) based model developed by us can facilitate rapid screening of large and diverse chemical libraries by reducing false hits and prioritising compounds before setting up expensive High Throughput Screening experiment. The SVM model, trained with molecular descriptors of proliferation inhibitors and non-inhibitors, displayed a satisfactory performance on cross validations and independent data set, with an average accuracy of 83% and AUC of 0.88. Intriguingly, the method displayed remarkable accuracy for the recently submitted P. falciparum whole cell screening datasets. The method also predicted several in...

Protein-protein interactions (PPI) are known to play an essential role between the neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor Ric8a to regulate synapse function, emerging as a druggable interface for synaptopathies such as the Fragile X syndrome (FXS). Recently, the phenothiazine FD44 has been identified as an inhibitor of this PPI, decreasing the abnormally high synapse number and enhancing associative learning in a FXS animal model. Here, we have integrated advanced experimental and computational studies to obtain important structural insights into Drosophila NCS-1/FD44 recognition to understand the basis of its affinity and specificity and generate improved PPI regulators. This has allowed the identification of a new small drug-like molecule, IGS-1.76, which efficiently inhibits the human NCS-1/Ric8a complex with improved binding potency. The crystal structure of the Drosophila NCS-1/IGS-1.76 complex demonstrates that the new inhibitor, although chemically ...

This work provides an affordable strategy to enhance the corrosion resistance of hydrotalcite coating by chemical modification of the coating with 2-mercaptobenzimidazole. The corrosion protection of the AS21 alloy immersed in Hank's solution is described by means of coatings containing Mg/Al hydrotalcites impregnated with the organic corrosion inhibitor 2-mercaptobenzimidazole (HT-2-MBI). The effect of the coating concentration on the efficiency of corrosion inhibition was determined using the techniques of electrochemical impedance spectroscopy and polarization curves. A maximum efficiency of 92% was reached after 0.5 hours and 75% in a period of 102 hours.

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