Design, Synthesis, Antibacterial, and Antifungal Evaluation of a New Series of Quinazoline-Thiazole and /or Quinazoline-Triazole Hybrids as Bioactive Heterocycles.

Herein, a one-pot reaction between cyclohexanone, thiourea, and 2,5-dimethoxybenzaldehyde allowed to prepare hexahydroquinazoline-2(1H)-thione 4 firstly, which dollowed by reacting with hydrazine hydrate to produce the corresponding 2-hydrazinylhexahydroquinazoline 6. Interesting analogs of thiazolo[3,2-a]quinazoline 7-13 where obtained when hexahydroquinazoline-2(1H)-thione 4 reacted with 1,2-dibromoethane, chloroacetyl chloride, bromoacetic acid, bromoacetic acid/4-chlorobenzaldehyde, 2-bromopropionic acid, ethyl bromocyanoacetate, and/or bromomalononitrile; respectively. While triazolo[4,3-a] quinazoline 14-16 were created when 2-hydrazinylhexahydroquinazoline 6 reacted with triethyl orthoformate, acetic anhydride, and carbon disulfide respectively. Additionally, the new analogs were examined for their antibacterial and antifungal properties against Escherichia coli, Staphylococcus aureus, and Candida albicans. It was discovered that triazolo[4,3-a] quinazoline analogs 14-16 have superior bacterial and fungal activity when compared to the corresponding conventional doses of Streptomycin and Griseofulvin. Towards Candida albicans; compounds 14, 15, and 16 increase activity with 1.14%, 1.15%, and 1.21%, respectively more than griseofulvin.While, for Staphylococcus aureus; compounds 14, 15, and 16 increase activity with 1.5%, 1.5%, and 1.7%, respectively more than streptomycin. Morever, for Escherichia coli; compounds 14, 15, and 16 increase activity with 1.19%, 1.21%, and 1.22%, respectively more than streptomycin. Finally, structure activity relationships show that quinazoline derivatives exhibit higher activity when fused to pyrazole ring 14-16 as compared when fused thiophene ring 7-13.

Spirothiazolidine-Derivative on Silver Nanoparticles and Carbon Nanotubes: Evaluation of Antibacterial, Anti-Fungal, Anti-Inflammatory, Antioxidant and Gastroprotective Activities.

This study aims to develop innovative heterocyclic nanocomposites incorporating silver nanoparticles (SNPs) for potential therapeutic applications targeting infections, gastric ulceration, inflammation, and oxidative damage. By synthesizing new derivatives of spiro-thiazolidine-carbonitrile (Py-ST-X) and incorporating them into Ag nanoparticles (AgNPs) and carbon nanotubes (CNTs), we have prepared Ag@Py-ST-X and Ag@Py-ST-X@CNT nanocomposites, respectively. The physical properties of these materials were studied using XRD, TEM, SEM, and Zeta potential techniques. In our investigation involving rats with gastric ulcers, we observed noteworthy inhibitory effects on gastric acid enzyme activity, specifically H+/K+ATPase, by Ag@Py-ST-NO2 and Ag@Py-ST-Br nanocomposites, demonstrating reductions of 25 and 34%, respectively, compared to untreated ulcers. Nanotubulation of these compounds further improved their inhibitory efficacy to 29 and 45%, respectively. Additionally, these nanoparticles showed the most potent myeloperoxidase (MPO)-inhibitory activity, demonstrating 36 and 49% inhibition, respectively, with nanotubulated versions reaching 44 and 53%. Moreover, Ag@Py-ST-NO2@CNT and Ag@Py-ST-Br@CNT nanotubes showed significant antioxidant activity, reducing thiobarbituric acid reactive substances (TBARS) by 35 and 51%, and hydrogen peroxide (H2O2) levels by 49 and 71%, respectively. These therapeutic effects were confirmed by reductions in gastric surface area (GSA) by 44% and 52%, a decrease in ulcer index (UI) from 80% to 44 and 38%, and an increase in curative index (CI) from 19 to 55 and 62% following administration of Ag@Py-ST-NO2@CNT and Ag@Py-ST-Br@CNT, respectively. Histological studies support these findings, suggesting the potential of these nanocomposites as promising candidates for treating various disorders.

Water scarcity in the Kingdom of Saudi Arabia.

Saudi Arabia (SA) is one of the world's arid, most water-scarce nations without permanent water resources. The purpose of this article is to provide a comprehensive overview of Saudi Arabia's water resources availability and reliability in terms of water supply, demand, and the major challenges that water faces. Saudi has an annual water supply of roughly 89.5 m3 per person as consumption is rising in parallel with the country's rapid population growth and development. SA produces the most desalinated seawater in the world, accounting for 22% of worldwide consumption. Due to changes in agricultural demand, Saudi Arabia's overall water needs in 2020 were 15.98 BCM. Apart from agricultural use, the food industry utilizes up to 80% of freshwater supplies, with only around 20% of rain recharging the aquifer, meaning that the region will still be water-stressed by 2025. In addition to wastewater reuse, water expenses should be split between private investors and the government, and water losses in cities should be collected and recycled. Water development projects must also be safeguarded and have long-term viability for the community's future and well-being. Despite previous conservation efforts (public awareness campaigns, television and other public media messages, drip irrigation, and so on), more work is required, including improving water resource infrastructure, implementing environmental use of friendly technologies, and increasing economic feasibility, social acceptability, and management in light of the Sustainable Development Goals (SDG).

New Epoxy and Hardener System Based on an Imidazolium Ionic Liquid as an Anticorrosive Coating for Steel in the Marine Environment.

The large sizes of cations and anions of organic salts are the driving force for the application of ionic liquids (organic salts) in harsh salty conditions. Moreover, the formation of crosslinked ionic liquid networks as anti-rust and anticorrosion protective films on the substrate surfaces repels seawater salt and water vapor from their surface to prevent corrosion. In this respect, an imidazolium epoxy resin and polyamine hardener as ionic liquids were prepared by the condensation of either pentaethylenehexamine or ethanolamine with glyoxal and p-hydroxybenzaldehyde or formalin in acetic acid as a catalyst. The hydroxyl and phenol groups of the imidazolium ionic liquid were reacted with epichlorohydrine in the presence of NaOH as a catalyst to prepare polyfunctional epoxy resins. The chemical structure, nitrogen content, amine value, epoxy equivalent weight, thermal characteristics, and stability of the imidazolium epoxy resin and polyamine hardener were evaluated. Moreover, their curing and thermomechanical properties were investigated to confirm the formation of homogeneous, elastic, and thermally stable cured epoxy networks. The corrosion inhibition and salt spray resistance of the uncured and cured imidazolium epoxy resin and polyamine as coatings for steel in seawater were evaluated.

First Synthesis for Bis-Spirothiazolidine Derivatives as a Novel Heterocyclic Framework and Their Biological Activity.

BACKGROUND: Spirothiazolidines are versatile synthetic scaffold possessing wide spectrum of biological interests involving potential anticancer activity. OBJECTIVE: To report the first synthesis of Bis Spiro-thiazolidine as a novel heterocyclic ring system. METHODS: One-pot three-component reaction including condensation of p-phenyllene diamine; cyclohexanone and thioglycolic acid produced Spiro-thiazolidine 4, which underwent further condensation with cyclohexanone and thioglycolic acid with equimolar ratio to introduce Bis-Spiothiazolidine 5 as the first synthesis. Also, bis spiro-thiazolidine arylidene derivatives 6-13 were synthesized by the reaction of Bis-Spiothiazolidine 5 with different aromatic benzaldehydes. RESULTS: Four compounds 13, 12, 9 and 11 have shown highly significant anticancer activity compared to Doxorubicin® (positive control) against Human liver carcinoma (HepG2) and Human Normal Retina pigmented epithelium (RPE-1) cell lines. CONCLUSION: The novel bis-spirothiazolidine deriviatives have been synthesized for the first time and showed excellent anticancer activities compare with the corresponding spirothiazolidine derivatives.

Development of a Novel Series of Anticancer and Antidiabetic: Spirothiazolidines Analogs.

4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 2-4. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the corresponding aminospirothiazolo pyridine-carbonitrile derivative 6 and spirothiazolopyridinone-carbonitrile derivative 7. Condensation of spirothiazolidine 1 with 4-chlorobenzaldehyde gave the corresponding spiro arylidiene derivative 8, which was utilized as a component of Micheal addition to react with excess of nitrogen nucleophiles to yield novel ring frameworks 4-(3'-(4-chlorophenyl)-spiro [cyclohexane-1,5'-pyrazolo[3,4-d]thiazol]-6'(1'H)-yl)aniline (9) and 4-(3'-(4-chlorophenyl)-6'H- spiro[cyclohexane-1,5'-thiazolo[5,4-d]isoxazol]-6'-yl)aniline (10). Finally, when spirothiazolo pyridinone-carbonitrile derivative 7 sodium salt generated in situ was reacted with different alkyl halides, it produced the corresponding N-derivatives 12-16. Three compounds, 6, 14, and 16, showed high significantly anticancer activities compared with Doxorubicin® (positive control) against human breast carcinoma (MCF-7) and human liver carcinoma (HepG-2) cell lines. On the other hand, compounds 6 and 9 showed higher therapeutic indices for both of alpha-amylase inhibitor and alpha-glucosidase inhibitor than the other tested compounds compared with the antidiabetic Acarbose (positive control).

Synthesis, Molecular Docking and in Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine⁻Pyrazole Hybrid Derivatives.

A series of novel pyridine and fused pyridine derivatives have been prepared starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3-carbonitrile 1 which on treatment with appropriate formic acid, acetic acid/ acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the corresponding triazolopyridine derivatives 2⁻5. Also, treatment of hydrazide 1 with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2-dichloroethane yielded the corresponding pyridotriazine derivatives 7⁻10. Further transformation of compound 1 with a different active methylene group, namely acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or ethyl acetoacetate, produced the pyridine⁻pyrazole hybrid derivatives 11⁻15. These newly synthesized compounds (1⁻15) were subjected to in silico molecular docking screenings towards GlcN-6-P synthase as the target protein. The results revealed moderate to good binding energies of the ligands on the target protein. All the newly prepared products exhibited antimicrobial and antioxidant activity.

Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs.

New [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo C-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation.

4-(2-(4-Halophenyl)hydrazinyl)-6-phenylpyridazin-3(2H)-ones 1a,b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2-4, respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7. The reaction of 4-(2-(4-chlorophenyl)hydrazinyl)-3-hydrazinyl-6-phenylpyridazine (7) with acetic anhydride, p-chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8-10. On the other hand, 5-(4-chlorophenylamino)-7-(3,5-dimethoxybenzylidene)-3-phenyl-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one (11) was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p-chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate) and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate) to afford the corresponding fused compounds 12-15, respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV) was performed for the new compounds. 4-(4-Chlorophenylamino)-6-phenyl-1,2-dihydropyridazino[4,3-e][1,2,4]triazine-3(4H)-thione (10) showed the highest effect against HAV.

Synthesis and Anticancer Activity of New 1-Thia-4-azaspiro[4.5]decane, Their Derived Thiazolopyrimidine and 1,3,4-Thiadiazole Thioglycosides.

New 1-thia-azaspiro[4.5]decane derivatives, their derived thiazolopyrimidine and 1,3,4-thiadiazole compounds were synthesized. The thioglycoside derivatives of the synthesized (1,3,4-thiadiazolyl)thiaazaspiro[4.5]decane and thiazolopyrimidinethione compounds were synthesized by glycosylation reactions using acetylated glycosyl bromides. The anticancer activity of synthesized compounds was studied against the cell culture of HepG-2 (human liver hepatocellular carcinoma), PC-3 (human prostate adenocarcinoma) and HCT116 (human colorectal carcinoma) cell lines and a number of compounds showed moderate to high inhibition activities.