Letters in Drug Design & Discovery - Volume 13, Issue 4, 2016

Background: Risk factors represented by genetic, environmental or social stress induce severe psychiatric disorders such as depression, schizophrenia or severe neurodegenerative processes. Antipsychotics are required for the pharmacological treatments of these disorders, but their molecular mechanisms and especially those involved in protecting the nervous system, are still unclear. The latest strategies in the neur Read More

Introduction: Aspartate transcarbamylase (ATCase) is involved in the initial steps of pyrimidine nucleotide biosynthesis and subject to regulation. Objective: Since Phenobarbital is an important drug, the current study focuses on a comparative investigation of the inhibition of bacterial and murine ATCase by some phenobarbital analogues. Methods: Phenobarbital analogues (thymidine, phenobarbital, and thiobarbituric acid) Read More

Lichen polyketides (1−14), isolated from Roccella montagnei and Parmotrema cooperi,were evaluated for their urease inhibitory potential. Compound 5 (methyl-β-orcinol carboxylate) was found to be the most potent inhibitor among the series with the IC50 = 17.4 ± 3.0 μM, as compared to the standard thiourea (IC50= 21.0±0.1 μM). SAR studies revealed that mononuclear polyketidesare more potent inhibitors Read More

Protein Tyrosine Phosphatase (PTP)-1B is a cytosolic receptor like PTPase, which plays an important role in treatment of type 2 diabetes mellitus (T2DM) via negative regulation of insulin signaling pathway. It is evident from the literature that biphenyl ring substituted compounds possess significant PTP-1B inhibitory activity due to extended interaction of the additional phenyl ring with the allosteric site of PTP-1B along with Read More

Activation of Notch signalling pathway is triggered by binding of NICD to transcription factor CSL and transcriptional co-activator MAML, which involves in various biological functions as well as progression of diseases. Recent prediction shows suppression of cancer causing genes of this pathway through inhibition of NICD-MAML interaction. Through virtual screening against “NCI Diversity 3” of Zinc database, we identified Read More

Blocking epidermal growth factor receptor (EGFR) has been the hotspot in the field of cancer therapy. Based on the fact that salicylanilides possess well inhibitory activity against EGFR tyrosine kinase, a series of salicylamide analogs bearing 4’-substitution were designed to explore new candidates exhibiting improved efficacy against EGFR. Many of the synthesized compounds inhibited EGFR in the micromolar range, esp Read More

A series of novel hydrazone derivatives containing pyridine moiety were designed and synthesized from 2,3-dichloro-5-(trifluoromethyl)pyridine as starting materials under microwave irradiation, and their structures were characterized by 1H NMR, MS and elemental analysis. The biological activity of title compounds was determined. The results indicated that some of title compounds exhibited good antifungal activity.

A series of substituted pyrimidinyl (thio)semicarbazide derivatives were designed and synthesized. The antitumor results showed that the activity of thiosemicarbazide compounds (series II) was generally higher than that of the corresponding semicarbazide derivatives (series I). Among them, IIk displayed higher cytotoxicity against HL-60, BGC-823 and Bel-7402 than that of adriamycin and exhibited broad in vitro cytotoxicity agai Read More

A series of novel C3-linked β -carboline pyridine (BCP) derivatives have been synthesized via modified Khronke reaction and studied for their DNA-binding affinities. Among all the derivatives, compound 12f has shown significant enhancement in the DNA-binding affinity (ΔTm: 6.3 °C and 6.5 °C at 0 h and 18 h incubation) in comparison to the standard Doxorubicin (ΔTm: 2.4 °C and 2.6 °C at 0 h and 18 h incubation). This result su Read More

A series of novel acetylated piperazine-containing N-glucosides and bis(Nglucoside) 8a-i were synthesized by the nucleophilic addition of acetylated glucopyranosyl isothiocyanate with various substituted piperazines in THF with high yields. Their novel deacetylated products 9a-i were also synthesized after Me- ONa/MeOH treatment. The preliminary bioassays for 18 novel title compounds showed that several compounds ha Read More