Design, synthesis and mechanistic study of new dual targeting HDAC/tubulin inhibitors.

The purpose of this work is to create and synthesize a new class of chemicals: 3-cyano-2-substituted pyridine compounds with expected multitarget inhibition of histone deacetylase (HDAC) and tubulin. The target compounds ( and ) were synthesized utilizing 6-(4-methoxyphenyl)-2-oxo-4-(3,4,5-trimethoxyphenyl)-3-cyanopyridine, with various linkers and zinc-binding groups (ZBGs). Most of the tested compounds showed promising growth inhibition, and hydroxamic acid-containing hybrids possessed higher HDAC inhibition than other ZBGs.

Discovery of new thiazolidine-2,4-dione derivatives as potential VEGFR-2 inhibitors: and studies.

In this study, a series of seven novel 2,4-dioxothiazolidine derivatives with potential anticancer and VEGFR-2 inhibiting abilities were designed and synthesized as VEGFR-2 inhibitors. The synthesized compounds were tested for their potential to inhibit VEGFR-2 and the growth of HepG2 and MCF-7 cancer cell lines. Among the compounds tested, compound (IC = 0.

Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies.

Structural-based drug design and solvent-free synthesis were combined to obtain three novel series of 5-arylethylidene-aminopyrimidine-2,4-diones (, -, ,), 5-arylethylidene-amino-2-thiopyrimidine-4-ones (,), and 6-arylpteridines (,) as dual BRD4 and PLK1 inhibitors. MTT assays of synthesized compounds against breast (MDA-MB-231), colorectal (HT-29), and renal (U-937) cancer cells showed excellent-to-good cytotoxic activity, compared to Methotrexate; MDA-MB-231 were the most sensitive cancer cells. The most active compounds were tested against normal Vero cells.

New thiazolidine-2,4-diones as effective anti-proliferative and anti-VEGFR-2 agents: Design, synthesis, in vitro, docking, MD simulations, DFT, ADMET, and toxicity studies.

Novel thiazolidine-2,4-dione derivatives, 11a-g, were designed, and synthesized targeting the VEGFR-2 protein. The in vitro studies indicated the abilities of the synthesized derivatives to inhibit VEGFR-2 and prevent the growth of two different cancer cell types, HepG2 and MCF-7. Compound 11 f exhibited the strongest anti-VEGFR-2 activity (IC = 0.

Synthesis, DFT calculations, and anti-proliferative evaluation of pyrimidine and selenadiazolopyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors.

Novel series of aminopyrimidines bearing a biologically active cyclohexenone and oxo-selaneylidene moiety , besides selenadiazolopyrimidines ( and ), were synthesised using 5,6-diaminouracils as starting materials. Compound exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC 14.31 ± 0.

Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-] pyrimidines as topoisomerase II inhibitors.

New thiazolopyrimidine derivatives and were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds and exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin.

()--(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide: A Novel Pyridine Derivative for Inhibiting Vascular Endothelial Growth Factor Receptor-2: Synthesis, Computational, and Anticancer Studies.

()--(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide (compound ) was designed as an antiangiogenic VEGFR-2 inhibitor with the essential pharmacophoric structural properties to interact with the catalytic pocket of VEGFR-2. The designed derivative was synthesized, and its structure was confirmed through Ms, elemental, H, and C spectral data. The potentiality of the designed pyridine derivative to bind with and inhibit the vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme was indicated by molecular docking assessments.

New Pyrimidine-5-Carbonitriles as COX-2 Inhibitors: Design, Synthesis, Anticancer Screening, Molecular Docking, and In Silico ADME Profile Studies.

Two series of cyanopyrimidine hybrids were synthesized bearing either benzo[]imidazole, benzo[]oxazole, benzo[]thiazole, and benzo[]thiophene derivatives via methylene amino linker - (Formula A) or various sulphonamide phenyl moieties - (Formula B) at the C-2 position. All compounds' cyclooxygenase COX-2 inhibitory activities were evaluated, and all synthesized compounds demonstrated potent activity at minimal concentrations, with IC values in the submicromolar range. Compounds , , and were discovered to be the most active pyrimidine derivatives, with the highest COX-2 percent inhibition and IC values being nearly equal to Celecoxib and approximately 4.

Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: and study.

Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.

New Triazinoindole Bearing Benzimidazole/Benzoxazole Hybrids Analogs as Potent Inhibitors of Urease: Synthesis, In Vitro Analysis and Molecular Docking Studies.

Twenty-four analogs based on triazinoindole bearing benzimidazole/benzoxazole moieties (-) were synthesized. Utilizing a variety of spectroscopic methods, including H-, C-NMR, and HREI-MS, the newly afforded compounds (-) were analyzed. The synthesized analogs were tested against urease enzyme (in vitro) as compared to the standard thiourea drug.

Synthesis of Novel 2,3-Dihydro-1,5-Benzothiazepines as α-Glucosidase Inhibitors: , , Kinetic, SAR, Molecular Docking, and QSAR Studies.

In the present study, a series of 2,3-dihydro-1,5-benzothiazepine derivatives - has been synthesized sand characterized by various spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using and mechanism-based assays. The tested compounds - exhibited inhibitory potential against α-glucosidase with IC = 2.

Regioselective One-Pot Synthesis, Biological Activity and Molecular Docking Studies of Novel Conjugates -(p-Aryltriazolyl)-1,5-benzodiazepin-2-ones as Potent Antibacterial and Antifungal Agents.

Novel 1,2,3-triazolo-linked-1,5-benzodiazepinones were designed and synthesized via a Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC). The chemical structures of these compounds were confirmed by H NMR, C NMR, HMBC, HRMS, and elemental analysis. The compounds were screened for their in vitro antibacterial and antifungal activities.