Synthesis, biological activities, and molecular docking studies of triazolo[4,3-b]triazine derivatives as a novel class of α-glucosidase and α-amylase inhibitors.

In diabetes mellitus, amylase and glucosidase enzymes are the primary triggers. The main function of these enzymes is to break macromolecules into simple sugar units, which directly affect blood sugar levels by increasing blood permeability. To overcome this metabolic effect, there is a need for a potent and effective inhibitor capable of suppressing the enzymatic conversion of sugar macromolecules into their smaller units.

Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives.

In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC value of 1.7 µM which is 100 folds stronger than positive control, acarbose.

Imidazo[1,2-a]quinazolines as novel, potent EGFR-TK inhibitors: Design, synthesis, bioactivity evaluation, and in silico studies.

Tyrosine protein kinases (TKs) have been proved to play substantial roles on many cellular processes and their overexpression tend to be found in various types of cancers. Therefore, over recent decades, numerous tyrosine protein kinase inhibitors particularly epidermal growth factor receptor (EGFR) inhibitors have been introduced to treat cancer. Present study describes a novel series of imidazo[1,2-a]quinazolines 18 as potential -inhibitors.

Synthesis of novel 2-acetamide-5-phenylthio-1,3,4-thiadiazole-containing phenyl urea derivatives as potential VEGFR-2 inhibitors.

A novel series of 2-acetamide-5-phenylthio-1,3,4-thiadiazol derivatives containing a phenyl urea warhead were synthesized and evaluated as antiproliferative agents. The cytotoxic activities of the newly synthesized compounds were evaluated toward three human cancer cell lines, including HT-29, A431, and PC3, as well as normal HDF cells, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The biological results revealed the highest degree of cytotoxic effects for the 4-chloro-containing compound 9e against the A431 cell line.

Pyrimidine-based EGFR TK inhibitors in targeted cancer therapy.

Despite significant improvements of new treatment options, cancer continues to represent as one of the most common and fatal disease. The EGFR signaling pathway is considered as a significant approach in targeted therapy of cancers. Blocking the EGFR-driven pathway by inhibiting the intracellular tyrosine kinase domain of EGFR have shown considerable improvement in cancer therapy.

Synthesis, in-vitro evaluation, molecular docking, and kinetic studies of pyridazine-triazole hybrid system as novel α-glucosidase inhibitors.

In this study, we reported the discovery of pyridazine based 1,2,3-triazole derivatives as inhibitors of α-glucosidase. All target compounds exhibited significant inhibitory activities against yeast and rat α-glucosidase enzymes compared to positive control, acarbose. The most potent compound 6j, ethyl 3-(2-(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)ethyl)-5,6-diphenylpyridazine-4-carboxylate exhibited IC values of 58, and 73 µM.

Quinazolin-4(3H)-one based agents bearing thiadiazole-urea: Synthesis and evaluation of anti-proliferative and antiangiogenic activity.

A series of quinazolin-4(3H)-one based agents containing thiadiazole-urea were designed, synthesized, and biologically evaluated. The proliferation rate of PC3 cells was moderately reduced by compound 9f (IC = 17.7 μM)which was comparable with sorafenib (IC = 17.

Design, synthesis, molecular docking study, and antibacterial evaluation of some new fluoroquinolone analogues bearing a quinazolinone moiety.

Background: Increasing bacterial resistance to quinolones is concerning. Hence, the development of novel quinolones by chemical modifications to overcome quinolone resistance is an attractive perspective in this context.

Objective: In this study, it is aimed to design and synthesize a novel series of functionalized fluoroquinolones using ciprofloxacin and sarafloxacin cores by hybridization of quinazolinone derivatives.

Synthesis and radioligand-binding assay of 2,5-disubstituted thiadiazoles and evaluation of their anticonvulsant activities.

In this study, a number of 2,5-disubstituted 1,3,4-thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital-induced sleep test. Compounds 7 (ED  = 1.

Design and synthesis of novel pyridazine N-aryl acetamides: In-vitro evaluation of α-glucosidase inhibition, docking, and kinetic studies.

We herein applied the four step-synthetic route to prepare the pyridazine core attached to the various N-aryl acetamides. By this approach, a new series of pyridazine-based compounds were synthesized, characterized and evaluated for their activities against α-glucosidase enzyme. In-vitro α-glucosidase assay established that twelve compounds are more potent than acarbose.

Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors.

A new series of compounds based on benzodiazepine-1,2,3-triazole were synthesized and evaluated as cholinesterase inhibitors by Ellman's method. The compounds proved to be selective inhibitors of butyrylcholinesterase (BuChE) over acetylcholinesterase. The most potent compound was 3,3-dimethyl-11-(3-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one, identified as a submicromolar inhibitor of BuChE with IC value of 0.

6-Cinnamoyl-4-arylaminothienopyrimidines as highly potent cytotoxic agents: Design, synthesis and structure-activity relationship studies.

In this paper, we described the synthesis and cytotoxic activities of two new series of thieno[2,3-d]pyrimidine and thieno[3,2-d] pyrimidine derivatives. Most of the synthesized compounds had significant antiproliferative activities against PC3, MDA-MB-231, A549, and HeLa cell lines in comparison to the reference drug, erlotinib. Compounds N-(4-((3,5-dichlorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)cinnamamide 8e and (E)-N-(4-((3,4-dichlorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-3-(4-methoxyphenyl)acrylamide 8g with IC values of 4 nM and 33 nM, respectively, against HeLa cell line were chosen for further studies.

2-(Bipiperidin-1-yl)-5-(nitroaryl)-1,3,4-thiadiazoles: Synthesis, evaluation of in vitro leishmanicidal activity, and mechanism of action.

The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of Leishmania major (L.