Coumarin-amino acid hybrids as promising anticancer agents: design, synthesis, docking studies and CK2 inhibition.

A series of mono-peptide, di-peptide and tri-peptide derivatives linked to a coumarin scaffold (5a-c, 7a-c, and 9a-c) were synthesized the azide-coupling method from corresponding hydrazides 4, 6, and 8. These compounds were tested for anticancer activity against HepG-2, PC-3, and Hct-116 cell lines. Compounds, 7c, and 5b showed significant cytotoxicity, outperforming doxorubicin, with IC values of 34.

Evidence on the inhibitory effect of Brassica plants against Acinetobacter baumannii lipases: phytochemical analysis, in vitro, and molecular docking studies.

Background: Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A.

New potential anti-SARS-CoV-2 and anti-cancer therapies of chitosan derivatives and its nanoparticles: Preparation and characterization.

Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP).

Hydrazone-based Materials; DFT, TD-DFT, NBO Analysis, Fukui Function, MESP Analysis, and Solar Cell Applications.

Due to numerous pharmaceutical and biological activities hydrazone (TC) based materials, it was important to investigate quantum chemical studies such as Density functional theory (DFT) calculations, natural bond orbital (NBO) analysis, molecular electrostatic potential (MESP), and local reactivity usage Fukui function for six TC derivatives compounds. DFT, NBO, MESP, and local reactivity calculations were obtained via utilizing CAM-Becke's three-parameter functional and Leee Yange Parr (CAM-B3LYP) functional and 6-311G +  + (2d, 2p) basis set. Optimized molecular structures for all studied compounds were obtained usage the DFT/CAM-B3LYP/6-311G +  + (2d, 2p) method.

Development of fluorinated nicotinonitriles and fused candidates as antimicrobial, antibiofilm, and enzyme inhibitors.

The antimicrobial assessments of two new series of nicotinonitriles and pyrido[2,3-d]pyrimidines were performed using amoxicillin and nystatin as reference standards. Outstanding antifungal activities were achieved by some target compounds; for instance, compounds 7 and 9 displayed a minimal inhibitory concentration (MIC) value of 1.95 µg/ml toward Candida albicans, compound 11 showed a potent anti-Rhizopus effect (MIC 1.

Design, Synthesis, biological Evaluation, and molecular docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers.

A series of novel hybrid pyrazolo[3,4-d]pyramidine derivatives was designed and chemically synthesized in useful yields. The synthesized compounds were structurally characterized by the usual techniques. All the new synthesized compounds were biologically screened in vitro for their antiproliferative activities against a panel of four cancer cell lines, namely HepG-2, MCF-7, HCT-116, and Hela.

Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies.

Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential.

Novel 1,2,4-triazole derivatives: Design, synthesis, anticancer evaluation, molecular docking, and pharmacokinetic profiling studies.

Three novel series of 1,2,4-triazole derivatives were designed and synthesized as potential adenosine A2B receptor antagonists. The design of the new compounds depended on a virtual screening of a previously constructed library of compounds targeting the human adenosine A2B protein. Spectroscopic techniques including H nuclear magnetic resonance (NMR) and C NMR, and infrared and mass spectroscopy were used to confirm the structures of the synthesized compounds.

Unravelling the anticancer potency of 1,2,4-triazole-N-arylamide hybrids through inhibition of STAT3: synthesis and in silico mechanistic studies.

The discovery of potent STAT3 inhibitors has gained noteworthy impetus in the last decade. In line with this trend, considering the proven biological importance of 1,2,4-triazoles, herein, we are reporting the design, synthesis, pharmacokinetic profiles, and in vitro anticancer activity of novel C3-linked 1,2,4-triazole-N-arylamide hybrids and their in silico proposed mechanism of action via inhibition of STAT3. The 1,2,4-triazole scaffold was selected as a privilege ring system that is embedded in core structures of a variety of anticancer drugs which are either in clinical use or still under clinical trials.

Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists.

Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses.

Antimicrobial screening and pharmacokinetic profiling of novel phenyl-[1,2,4]triazolo[4,3-a]quinoxaline analogues targeting DHFR and E. coli DNA gyrase B.

A novel series of [1,2,4]triazolo[4,3-a]quinoxaline derivatives of different heteroaromatization members were synthesized. The newly synthesized molecules were explored for their potential antimicrobial activities against a panel of pathogenic organisms. Among these derivatives, the chalcone compound 6e with a methoxy substituent exhibited broad potent antimicrobial activity against most of the bacterial and fungal strains.

Design, synthesis and anticancer evaluation of 1H-pyrazolo[3,4-d]pyrimidine derivatives as potent EGFR and EGFR inhibitors and apoptosis inducers.

In our attempt to develop effective EGFR-TKIs, two series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated in vitro for their inhibitory activities against EGFR. Compounds 15, 15, and 18 potently inhibited EGFR at sub-micro molar IC values comparable to that of erlotinib.

Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents.

Thymidylate synthase (TS), one of folate-dependent enzymes, is a key and well-recognized target for anticancer agents. In this study, a series of 6-aryl-5-cyano thiouracil derivatives were designed and synthesized in accordance with essential pharmacophoric features of known TS inhibitors. Nineteen compounds were screened in vitro for their anti-proliferative activities toward HePG-2, MCF-7, HCT-116, and PC-3 cell lines.

The second extracellular loop of GPCRs determines subtype-selectivity and controls efficacy as evidenced by loop exchange study at A2 adenosine receptors.

The second extracellular loop (EL2) of G protein-coupled receptors (GPCRs), which represent important drug targets, may be involved in ligand recognition and receptor activation. We studied the closely related adenosine receptor (AR) subtypes A2A and A2B by exchanging the complete EL2 of the human A2BAR for the EL2 of the A2AAR. Furthermore, single amino acid residues (Asp148(45.

Ligand-specific binding and activation of the human adenosine A(2B) receptor.

Adenosine A(2B) receptors, which play a role in inflammation and cancer, are of considerable interest as novel drug targets. To gain deeper insights into ligand binding and receptor activation, we exchanged amino acids predicted to be close to the binding pocket. The alanine mutants were stably expressed in CHO cells and characterized by radioligand binding and cAMP assays using three structural classes of ligands: xanthine (antagonist), adenosine, and aminopyridine derivatives (agonists).

Homology modelling of the human adenosine A2B receptor based on X-ray structures of bovine rhodopsin, the beta2-adrenergic receptor and the human adenosine A2A receptor.

A three-dimensional model of the human adenosine A2B receptor was generated by means of homology modelling, using the crystal structures of bovine rhodopsin, the beta2-adrenergic receptor, and the human adenosine A2A receptor as templates. In order to compare the three resulting models, the binding modes of the adenosine A2B receptor antagonists theophylline, ZM241385, MRS1706, and PSB601 were investigated. The A2A-based model was much better able to stabilize the ligands in the binding site than the other models reflecting the high degree of similarity between A2A and A2B receptors: while the A2B receptor shares about 21% of the residues with rhodopsin, and 31% with the beta2-adrenergic receptor, it is 56% identical to the adenosine A2A receptor.