Synthesis of novel pyridine and pyrazolyl pyridine conjugates with potent cytotoxicity against HepG2 cancer cells as PIM-1 kinase inhibitors and caspase activators.

A novel series of nicotinonitrile and pyrazolyl nicotinonitrile were synthesized, and their PIM-1 kinase inhibitors and caspase activators were investigated. New Manich bases 6-8 were synthesized reaction of pyridine 4 with piperidine, dimethyl amine, and morpholine in the presence of formalin. On the other hand, the pyrazolyl analogues 10-12 were synthesized heterocyclization of acetohydrazide derivative 9 with acetylacetone, malononitrile, and ethyl cyanoacetate, respectively, in ethanol.

Synthesis of -Alkyl-3-[2-oxoquinolin-1(2)-yl]propanoic Acid Derivatives and Related Compounds: Cytotoxicity and EGFR Inhibition of Some Propanamide Derivatives.

A series of 20 new structure-modified quinolin-2-one derivatives were prepared for biological evaluation. This was successfully achieved based on chemoselective reactions of heterocyclic amides with acrylic acid derivatives, which gave 3-[2-oxoquinolin-1-(2)-yl] propanoic acid derivatives (N-substitution via a unique behavior). The ester was reacted with hydrazine to afford the corresponding hydrazide.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective -alkylation addition reaction of 4-benzylphthalazin-1(2)-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c.

Synthesis of phthalazine-based derivatives as selective anti-breast cancer agents through EGFR-mediated apoptosis: in vitro and in silico studies.

The parent 2-(4-benzyl-1-oxophthalazin-2(1H)-yl)-acetohydrazide (4) has twenty-nine compounds. The starting material for their corresponding mono, dipeptides and reactions with active methylene compounds were produced by chemoselective N-alkylation of 4-Benzyl-2H-phthalazin-1-one (2) with ethyl chloroacetate to afford (4-benzyl-1-oxo-1H-phthalazin-2-yl) methyl acetate (3). The ester 3 was hydrazinolyzed to give hydrazide 4, then azide 5 coupled with amino acid ester hydrochloride and/or amines to produce several monopeptides, then the methyl (2-(4-benzyl-1-oxophthalazin-2(1H)-yl) acetyl) glycinate (7a) was hydrazinolyzed to produce corresponding hydrazide 2-(4-benzyl-1-oxophthalazin-2(1H)-yl)-N-(2-hydrazineyl-2-oxo ethyl) acetamide (8a).

Nephroprotective effects of Acacia senegal against aflatoxicosis via targeting inflammatory and apoptotic signaling pathways.

Aflatoxin B (AFB1) is a common environmental pollutant that poses a major hazard to both humans and animals. Acacia senegal (Gum) is well-known for having antioxidant and anti-inflammatory bioactive compounds. Our study aimed to scout the nephroprotective effects of Acacia gum (Gum) against AFB1-induced renal damage.

Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition.

Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the ,-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding.

Transformation of Amides to Thioamides Using an Efficient and Novel Thiating Reagent.

A convenient protocol was developed for the transformation of -aryl-substituted benzamides to -aryl-substituted benzothioamides using -isopropyldithiocarbamate isopropyl ammonium salt as a novel thiating reagent. The major advantages of this protocol are its procedure, short reaction times, mild conditions, simple work-up, high yields and pure products.

Zinc Oxide Nanoparticles and Synthesized Pyrazolopyrimidine Alleviate Diabetic Effects in Rats Induced by Type II Diabetes.

Diabetes mellitus (DM) is a category of metabolic illness characterized by high blood sugar levels and insufficient pancreatic insulin production or activity within the body. The most common type of diabetes is type II diabetes, which is a metabolic condition characterized by insulin resistance and pancreatic islet β-cell failure, resulting in hyperglycemia. The goal of this study was to examine the anti-diabetic implications of zinc oxide nanoparticles (ZnO NPs) and/or pyrazolopyrimidine in type II diabetic rats.

Convenient Synthesis of -Alkyl-2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetamides and Methyl-2-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetylamino]alkanoates.

A series of 27 new quinoxaline derivatives (-alkyl-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)]acetamides, methyl-2-[2-(3-phenylquinoxalin-2-ylsulfanyl)-acetylamino]alkanoates, and their corresponding dipeptides) were prepared from 3-phenylquinoxaline-2(1)-thione based on the chemoselective reaction with soft electrophiles. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the efficacy of 27 compounds on cancer cell viability and proliferation. A total of 13 compounds (-, , , , , , , , , , and ) showed inhibitory action on HCT-116 cancer cells and 15 compounds (-, , , , , , , , , , , , and ) showed activity on MCF-7 cancer cells, with compound exhibiting the highest inhibitory action (IC 1.

Arabic Gum Could Alleviate the Aflatoxin B-provoked Hepatic Injury in Rat: The Involvement of Oxidative Stress, Inflammatory, and Apoptotic Pathways.

Aflatoxin B (AF) is an unavoidable environmental pollutant that contaminates food, feed, and grains, which seriously threatens human and animal health. Arabic gum (AG) has recently evoked much attention owing to its promising therapeutic potential. Thus, the current study was conducted to look into the possible mechanisms beyond the ameliorative activity of AG against AF-inflicted hepatic injury.

Synthesis of Novel Phthalazinedione-Based Derivatives with Promising Cytotoxic, Anti-bacterial, and Molecular Docking Studies as VEGFR2 Inhibitors.

The parent ester methyl-3-[2-(4-oxo-3-phenyl-3,4-dihydro-phthalazin-1-yloxy)-acetylamino] has 18 compounds. The starting material for alkanoates, their corresponding hydrazides, hydrazones, and dipeptides were produced by chemoselective O-alkylation of 2-phenyl-2,3-dihydrophthalazine-1,4-dione with ethyl chloroacetate(4-oxo-3-phenyl-3,4-dihydro-phthalazin-1-yloxy) acetic acid methyl ester. The starting ester was hydrazinolyzed, then azide coupled with amino acid ester hydrochloride to produce several parent esters, and then hydrazinolyzed to produce parent hydrazides.

Assessment of Wheat Germ Oil Role in the Prevention of Induced Breast Cancer in Rats.

Breast cancer is the most predominant cause of death in women globally. The current study was performed to evaluate the possible protective role of wheat germ oil (WGO), wheat germ powder (WGP), and vitamin E (Vit E) against breast carcinoma induced by the environmental carcinogen 7,12-dimethylbenz[]anthracene (DMBA) in Sprague Dawely albino rats. Eighty female rats were divided into eight groups, each of ten rats.

Synthesis and Cytotoxic Activity of Novel Metal Complexes Derived from Methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate as Potential CDK8 Kinase Inhibitors.

Several metal complexes of methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate derivatives were synthesized and tested for their anti-tumor activities. The ligands include 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoic acid (), 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanehydrazide (), and 3-(4-chlorophenyl)-'-(4-(dimethylamino)benzylidene)-3-hydroxy-2,2-dimethylpropanehydrazide (). The ligands were reacted with Cu (II), Ni (II), and La (III) ions.

Synthesis and Biological Activities of Some New Benzotriazinone Derivatives Based on Molecular Docking; Promising HepG2 Liver Carcinoma Inhibitors.

In one-pot strategy, diazotization of methyl anthranilate followed by addition of amino acid ester hydrochloride, we have prepared methyl-2-(4-oxobenzotriazin-3(4)-yl)alkanoates -. Starting with hydrazides ,, -alkyl-2-(4-oxobenzotriazin-3(4)-yl)alkanamides -(-) and methyl-2-(2-(4-oxobenzotriazin-3(4)-yl)alkanamido)alkanoates -(-) were prepared via azide coupling. Hydrazones - were prepared via condensation of hydrazides , with 4-methoxybenzaldehyde, 4-dimethylaminobenzaldehyde, and/or arabinose.

Newly synthesized 3-(4-chloro-phenyl)-3-hydroxy-2,2-dimethyl-propionic acid methyl ester derivatives selectively inhibit the proliferation of colon cancer cells.

A series of 24 compounds were synthesized based on structure modification of the model methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate as potent HDACIs. Saponification and hydrazinolysis of the model ester afforded the corresponding acid and hydrazide, respectively. The model ester was transformed into the corresponding trichloroacetimidate or acetate by the reaction with trichloroacetonitrile and acetic anhydride, respectively.

Convenient Synthesis and Anticancer Activity of Methyl 2-[3-(3-Phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and -Alkyl 3-((3-Phenyl-quinoxalin-2-yl)sulfanyl)propanamides.

A series of methyl 2-[3-(3-phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and their corresponding hydrazides and -alkyl 3-((3-phenylquinoxalin-2-yl)sulfanyl)propanamides were prepared on the basis of the chemoselective Michael reaction of acrylic acid with the parent substrate 3-phenylquinoxaline-2(1)-thione. The parent thione was produced by a convenient novel thiation method from the corresponding 3-phenylquinoxalin-2(1)-one. The chemical structures of the newly synthesized compounds were confirmed by elemental analyses, H and C NMR.