Novel guanidine derivatives targeting leukemia as selective Src/Abl dual inhibitors: Design, synthesis and anti-proliferative activity.

A new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, H-, C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines.

Tailored Tetrasubstituted Imidazole Carrying the Benzenesulfonamide Fragments as Selective Human Carbonic Anhydrase IX/XII Inhibitors.

A new series of tetrasubstituted imidazole carrying sulfonamide as zinc-anchoring group has been designed. The structures of the synthesized derivatives 5 a-l have been confirmed by spectroscopic analysis. These compounds incorporate an ethylenic spacer between the benzenesulfonamide and the rest of the trisubstituted imidazole moiety and were tested as inhibitors of carbonic anhydrases and for in-vitro cytotoxicity.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds and ) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds -, -, -, and -. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c.

Nickel-hydroxide-encapsulated polyacrylamide as a novel adsorptive composite for the capture of methylene blue from wastewater.

The wastewater released from different industries is a major environmental issue that has grabbed significant attention lately. Thus, the implementation of suitable routes for the treatment of such water is strongly recommended to reach the level of possible reuse for either industrial or agricultural purposes. In line with such a concept, this research work introduces a new composite structure made the coating of polyacrylamide by loading nickel hydroxide nanoparticles for use as an absorbent for the purification of wastewater from dye contaminants.

Decoration of polystyrene with nanoparticles of cobalt hydroxide as new composites for the removal of Fe(iii) and methylene blue from industrial wastewater.

Effluent water from different industries is considered one of the most serious environmental pollutants due to its non-safe disposal. Therefore, proper treatment methods for such wastewater are strongly stimulated for its potential reuse in industries or agriculture. This study introduces a composite fabricated doping of polystyrene with nanoparticles of cobalt hydroxide as a novel adsorbent for dye and heavy metal decontamination from wastewater.

Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition.

The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine.

Anticancer Activities of Tetrasubstituted Imidazole-Pyrimidine-Sulfonamide Hybrids as Inhibitors of EGFR Mutants.

A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In-vitro screening of these hybrids against a full 60-cell-line panel at a single dose of 10 μM showed significant growth inhibition of up to 95 %. The most active compound showed in-vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR.

Structure-based design, synthesis, and biological evaluation of novel piperine-resveratrol hybrids as antiproliferative agents targeting SIRT-2.

A series of novel piperine-resveratrol hybrids 5a-h was designed, synthesized, and structurally elucidated by IR, and H, C, and F NMR. Antiproliferative activities of 5a-h were evaluated by NCI against sixty cancer cell lines. Compound 5b, possessing resveratrol pharmacophoric phenolic moieties, showed a complete cell death against leukemia HL-60 (TB) and Breast cancer MDA-MB-468 with growth inhibition percentage of -0.

A Polymer-based Monolithic Capillary Column with Polymyxin-B Chiral Selector for the Enantioselective Nano-High Performance Liquid Chromatographic Pharmaceutical Analysis.

Herein, we report the first use of Polymyxin-B antibiotic as a enantio-selector in polymer monolithic capillary. The capillaries were functionalised, characterized and tested for the enantioselective nano-HPLC separation of 50 racemic pharmaceutical drugs. They have been easily prepared by immobilizing Polymyxin-B over the organic polymer for 48 h (P1) or encapsulating Polymyxin-B within the organic polymer (P2) and tested for the enantioselective resolution of racemic drugs.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Fluorinated Candidates as PI3K Inhibitors: Targeting Fluorophilic Binding Sites.

Highly fluorinated candidates containing anticancer pharmacophores like thiosemicarbazone (-) and its cyclic analogues hydrazineylidenethiazolidine (-), 2-aminothiadiazole (-), and 2-hydrazineylidenethiazolidin-4-one (-) were synthesized, and their cytotoxic activity was assayed against 60 tumor cell lines. Compounds , , and displayed the most potent activity with lower toxic effects on MCF-10a. phosphatidylinositol 3-kinase (PI3K) enzyme inhibition was performed.

Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes.

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2'-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, H NMR, C NMR, UV-VIS, mass spectra, and thermal analysis.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors.

A novel series of tri-aryl imidazole derivatives - carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA and activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of > > > > > (Ki = 0.3-1.

Daptomycin: A Novel Macrocyclic Antibiotic as a Chiral Selector in an Organic Polymer Monolithic Capillary for the Enantioselective Analysis of a Set of Pharmaceuticals.

Daptomycin, a macrocyclic antibiotic, is here used as a new chiral selector in preparation of chiral stationary phase (CSP) in a recently prepared polymer monolithic capillary. The latter is prepared using the copolymerization of the monomers glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in the presence of daptomycin in water. Under reversed phase conditions (RP), the prepared capillaries were tested for the enantioselective nanoliquid chromatographic separation of fifty of the racemic drugs of different pharmacological groups, such as adrenergic blockers, H1-blockers, NSAIDs, antifungal drugs, and others.

Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors.

A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using H NMR, C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds were screened in vitro against Gram-positive bacterial strains such as and and Gram-negative strains such as and . As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria.

Design, synthesis, biological evaluation, and computational studies of novel thiazolo-pyrazole hybrids as promising selective COX-2 inhibitors: Implementation of apoptotic genes expression for ulcerogenic liability assessment.

A novel series of thiazolo-pyrazole hybrids has been prepared and assessed for their in vitro COX-1/COX-2 inhibitory activity. Compound 6c exhibited the most selective COX-2 inhibition profile (SI of 264) not far of Celecoxib (294). In-vivo anti-inflammatory activity revealed that compound 6d exhibited the highest activity (97.

JNK signaling as a target for anticancer therapy.

The JNKs are members of mitogen-activated protein kinases (MAPK) which regulate many physiological processes including inflammatory responses, macrophages, cell proliferation, differentiation, survival, and death. It is increasingly clear that the continuous activation of JNKs has a role in cancer development and progression. Therefore, JNKs represent attractive oncogenic targets for cancer therapy using small molecule kinase inhibitors.

Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies.

Two new series of 1,3,4-oxadiazole and coumarin derivatives based on pyrimidine-5-carbonitrile scaffold have been synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds 10c, 10e, 10h-j, 14e-f, 14i and 16 were found to be the most potent and selective inhibitors of COX-2 (IC 0.041-0.

Design, synthesis and antiproliferative evaluation of new tricyclic fused thiazolopyrimidines targeting topoisomerase II: Molecular docking and apoptosis inducing activity.

A novel series of thiazolopyrimidines and fused thiazolopyrimidines was designed and synthesized as topoisomerase II alpha inhibitors. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for anticancer activity against 60 human cancer cell lines representing the following cancer types: leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancers. Compound 3a was found to be the most potent inhibitor on renal cell line (A-498) causing 83.

Design, synthesis and molecular modeling of novel aryl carboximidamides and 3-aryl-1,2,4-oxadiazoles derived from indomethacin as potent anti-inflammatory iNOS/PGE2 inhibitors.

The development of NSAIDs/iNOS inhibitor hybrids is a new strategy for the treatment of inflammatory diseases by suppression of the overproduction of PGE and NO. A novel series of aryl carboximidamides 4a-g and their cyclized 3-aryl-1,2,4-oxadiazoles 5a-g counterparts derived from indomethacin 1 were synthesized. Most of the target compounds displayed lower LPS-induced NO production IC in RAW 264.

Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation.

A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed.

Design, synthesis and anticonvulsant activity of new imidazolidindione and imidazole derivatives.

New imidazolidindiones and tetra-substituted imidazole derivatives were designed, synthesized, and evaluated for the anticonvulsant activity through pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) tests using valproate sodium and phenytoin sodium as reference drugs, respectively. Most of the target compounds showed excellent activity against pentylenetetrazole (PTZ)-induced seizures with fair to no-activity against MES. Compounds 3d, 4e, 11b, and 11e showed higher activity (120%) than that of valproate sodium in PTZ model.

Design, synthesis and antitrypanosomal activity of heteroaryl-based 1,2,4-triazole and 1,3,4-oxadiazole derivatives.

Two series of novel 1,2,4-triazol-3-yl-thioacetamide 3a-b and 4a-b and 5-pyrazin-2-yl-3H-[1,3,4]oxadiazole-2-thiones 9a-h were designed and synthesized. The compounds prepared have been identified using H NMR, C NMR and elemental analyses. The synthesized compounds 3a, 3b, 4a, 4b, 9a, 9b, 9d-e and 9f have been evaluated with α-difluoromethylornithine (DFMO) as a control drug for their in vitro antitrypanosomal activity against Trypanosoma brucei.

Synthesis and characterization of new Cr(III), Fe(III) and Cu(II) complexes incorporating multi-substituted aryl imidazole ligand: Structural, DFT, DNA binding, and biological implications.

Designing new metal-based molecular antibiotics is an efficient approach to overcome the growing threat of antimicrobial resistance. In this paper, novel Cr(III), Fe(III) and Cu(II) complexes comprising substituted aryl imidazole ligand (MSEB), namely (2-(1-(2-hydroxyethyl)-4,5-diphenyl-1H-imidazole-2-yl)(4-bromophenol)) have been synthesized and characterized using infra-red (IR), ultraviolet-visible (UV-Vis) and H, C NMR spectroscopic techniques, together with elemental (CHN) and thermogravimetric analyses, molar conductance, and magnetic susceptibility measurements. The combined results along with the DFT calculations revealed a 1:1 (M: L) stoichiometric ratio and the complexes adopted distorted-octahedral geometries to afford [Cr(MSEB)Cl(HO)], [Fe(MSEB)(NO)(HO)] and [Cu(MSEB)Cl(HO)] respectively.

Specific stability indicating spectrofluorimetric method for determination of ledipasvir in the presence of its confirmed degradation products; application in human plasma.

A rapid and specific spectrofluorimetric method with higher sensitivity was developed for determination of ledipasvir (LDS) in tablets and human plasma. The proposed method relies on hydrogen bonding formations between the hydroxyl groups of polyoxyethylene 50 stearate and LDS, causing significant enhancement of its native fluorescence. The fluorescence intensity was measured at 430 nm after excitation at 340 nm.