Design, Synthesis, Pharmacological Evaluation of Quinazolin-4(3)-Ones Bearing Urea Functionality as Potential VEGFR-2 Inhibitors.

Background: In response to the urgent need for continuous discovery of new anti-proliferative agents, a new series of quinazoline compounds was prepared.

Methods: As a reference, four cancer cell lines-HCT116, HePG2, Hela, and MCF-7-and sorafenib (SOR) were used to assess the novel motifs' in vitro anticancer efficacy. The most cytotoxic compounds were tested in a VEGFR-2 suppressive test and flow cytometric test.

Identification of Benzothiazoles Bearing 1,3,4-Thiadiazole as Antiproliferative Hybrids Targeting VEGFR-2 and BRAF Kinase: Design, Synthesis, BIO Evaluation and In Silico Study.

Cancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class of targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and insights.

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid () was found to inhibit AR in a non-competitive manner (0.

Anti-inflammatory effect of 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole derivatives as p38α inhibitors.

In the present work, the anti-inflammatory effect of 30 compounds containing 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole was investigated. All final target compounds showed significant Inhibitory effect on p38α. P38α is considered one of the key kinases in the inflammatory process due to its regulatory effect on pro-inflammatory mediators.

Development of Olive Oil Containing Phytosomal Nanocomplex for Improving Skin Delivery of Quercetin: Formulation Design Optimization, In Vitro and Ex Vivo Appraisals.

The objective of the current work was to fabricate, optimize and assess olive oil/phytosomal nanocarriers to improve quercetin skin delivery. Olive oil/phytosomal nanocarriers, prepared by a solvent evaporation/anti-solvent precipitation technique, were optimized using a Box-Behnken design, and the optimized formulation was appraised for in vitro physicochemical characteristics and stability. The optimized formulation was assessed for skin permeation and histological alterations.

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and study.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione , 1,3,4-thiadiazole aryl urea and cyanothiouracil moieties was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, was the most potent showing IC50 of 5.

Phenylboronic Acid-Grafted Chitosan Nanocapsules for Effective Delivery and Controllable Release of Natural Antioxidants: Olive Oil and Hydroxytyrosol.

Olives and virgin olive oil (VOO) are a staple of Mediterranean diets and are rich in several beneficial phenolic compounds, including hydroxytyrosol (HT). Therefore, VOO was extracted from Koroneiki olive fruits, and its volatile as well as phenolic components were identified. Meanwhile, in order to upgrade the pharmaceutical capabilities of VOO and HT, a new conjugate phenylboronic acid-chitosan nanoparticles (PBA-CSNPs, NF-1) was fabricated and applied as nanocapsules for implanting high loading and efficient delivery of VOO and HT nanoformulations (NF-2 and NF-3).

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (, 1,3,4-thiadiazoles (-, and pyrimidines (-, was preparedand assessed for its potential COX-2 inhibitors. Compared to Celecoxib, compounds and were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds and were chosen among these most potent derivatives for further investigation.

X-ray Structures and Computational Studies of Two Bioactive 2-(Adamantane-1-carbonyl)--substituted Hydrazine-1-carbothioamides.

Two biologically active adamantane-linked hydrazine-1-carbothioamide derivatives, namely 2-(adamantane-1-carbonyl)--(-butyl)hydrazine-1-carbothioamide) and 2-(adamantane-1-carbonyl)--cyclohexylhydrazine-1-carbothioamide have been synthesized. X-ray analysis was conducted to study the effect of the -butyl and cyclohexyl moieties on the intermolecular interactions and conformation of the molecules in the solid state. X-ray analysis reveals that compound exhibits folded conformation, whereas compound adopts extended conformation.

Weak Noncovalent Interactions in Three Closely Related Adamantane-Linked 1,2,4-Triazole -Mannich Bases: Insights from Energy Frameworks, Hirshfeld Surface Analysis, 11β-HSD1 Molecular Docking and ADMET Prediction.

Structural analysis and docking studies of three adamantane-linked 1,2,4-triazole -Mannich bases (-) are presented. Compounds , and crystallized in the monoclinic 2/, 2 and 2/ space groups, respectively. Crystal packing of was stabilized by intermolecular C-H⋯O interactions, whereas compounds and were stabilized through intermolecular C-H⋯N, C-H⋯S and C-H⋯π interactions.

Combination of ligand and structure based virtual screening approaches for the discovery of potential PARP1 inhibitors.

Poly (ADP-ribose) polymerase 1 (PARP1) has high therapeutic value as biomolecular target for research and development of small molecules with antineoplastic activity, since it is upregulated in many cancers, especially in ovarian and BRCA 1/2 mutated breast cancers. Decades of investigation of PARP inhibitors (PARPi) have led to the approval of several drug compounds, however clinical application of PARPi in cancer therapy is limited due to a number of factors, including low selectivity, weak affinity and undesired side effects. Thus, identification of novel drug-like chemical compounds with alternatives to the known PARPi chemical scaffolds, binding modes and interaction patterns with amino acid residues in the active site is of high therapeutic importance.

Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery.

The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC).

Design, Synthesis and Anticancer Profile of New 4-(1-benzo[]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect.

A new series of 4-(1-benzo[]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that , and exhibited the strongest inhibitory activity among all target compounds and had the lowest IC of 0.

Supramolecular Self-Assembly Built by Weak Hydrogen, Chalcogen, and Unorthodox Nonbonded Motifs in 4-(4-Chlorophenyl)-3-[(4-fluorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4-1,2,4-triazole, a Selective COX-2 Inhibitor: Insights from X-ray and Theoretical Studies.

A selective triazole-based COX-2 inhibitor, 4-(4-chlorophenyl)-3-[(4-fluorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4-1,2,4-triazole, CHClFNS, has been synthesized, and its crystal structure was determined at 150 K. Single-crystal X-ray diffraction analysis revealed that the thiophene ring was disordered over two orientations. The crystal structure is stabilized by weak hydrogen and chalcogen bonds and unorthodox F···π and S···C(π) contacts.

Regioselective Rearrangement of 4,4-Disubstituted 2-Hydroxycyclohexa-2,5-Dienones under Deoxyfluorination Conditions.

The dienone-phenol rearrangement is a useful tool for the synthesis of highly substituted phenols. In our previous study of the rearrangement of 4,4-disubstituted 2-hydroxycyclohexa-2,5-dienone under deoxyfluorination conditions, bond migration proceeded with very poor regioselectivity. In this paper, an acid-mediated rearrangement of O-perfluoroalkylsulfonyl difluorides with regioselective migration toward the β'-carbon is reported.

Immunohistochemical expression of COX2 and iNOS in bladder cancer and its association with urinary schistosomiasis among Sudanese patients.

Aims: The purpose of this study was to determine if any relationship exists between expression of COX2 and iNOS markers and urinary schistosomiasis in bladder cancers.

Methodology: Immunohistochemical expression of COX2 and iNOS was assessed in formalin fixed paraffin wax processed tissues obtained from 155 patients with bladder cancers (87 SCC and 68 TCC) and 39 patients with benign bladder cystitis.

Results: The overall immune-expressions of COX2 and iNOS were 71.