Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities.

Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.

Cholinesterase Inhibitory Activities of N-Phenylthiazol-2-Amine Derivatives and their Molecular Docking Studies.

Alzheimer's disease (AD) is a type of neurodegenerative disorder which is responsible for many cognitive dysfunctions. According to the most accepted cholinergic hypothesis, cholinesterases have a major role in AD symptoms. The use of small molecules as inhibitors is one of the most useful strategies to control AD. In the present work, a series of N-phenylthiazol-2-amine derivatives was screened against acetylcholinesterase (AChE) from Electrophorus electricus and butyrylcholinesterase (BChE) from horse serum by using Ellman's method, using neostigmine and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors for AChE and BChE activity. N-(2,3-dimethylphenyl)thiazol-2-amine, 3j was found to be the most active inhibitor among the series with IC50 value of 0.009 ± 0.002 µM and 0.646 ± 0.012 µM against AChE and BChE, respectively. Molecular docking studies were carried out in order to better understand the ligand binding site interactions.

Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases.

The present study reports the synthesis of cinnamide derivatives and their biological activity as inhibitors of both cholinesterases and anticancer agents. Controlled inhibition of brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases (AD). The anticholinesterase activity of phenylcinnamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE with an IC50 0.29 ± 0.21 µM whereas 3-(2-chloro-6-nitrophenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of hBChE having IC50 1.18 ± 1.31 µM. To better understand the enzyme-inhibitor interaction of the most active compounds toward cholinesterases, molecular modelling studies were carried out on high-resolution crystallographic structures. The anticancer effects of synthesized compounds were also evaluated against cancer cell line (lung carcinoma). The compounds may be useful leads for the design of a new class of anticancer drugs for the treatment of cancer and cholinesterase inhibitors for Alzheimer's disease (AD).

Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors.

Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 µM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.