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Quinazoline and quinazolinone derivatives piqued medicinal chemistry interest in developing novel drug candidates owing to their pharmacological potential. They are important chemicals for the synthesis of a variety of physiologically significant and pharmacologically useful molecules. Quinazoline and quinazolinone derivatives have anticancer, anti-inflammatory, antidiabetic, anticonvulsant, antiviral, and antimicrobial potential. The increased understanding of quinazoline and quinazolinone derivatives in biological activities provides opportunities for new medicinal products. The present review focuses on novel advances in the synthesis of these important scaffolds and other medicinal aspects involving drug design, structure-activity relationship, and action mechanisms of quinazoline and quinazolinone derivatives to help in the development of new quinazoline and quinazolinone derivatives., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Pyrazole heterocycle is regarded as an extremely significant agent for the therapy of inflammation. Celecoxib, lonazolac, deracoxib, and phenylbutazone are examples of commercially approved pyrazole drugs with COX-2 inhibitory potential for curing inflammation. There have been recently many reviews for the biological significance of pyrazole derivatives. This review talks about pyrazole derivatives with anti-inflammatory activity and also sheds the light on the recent updates on pyrazole research with an emphasis on some synthetic pathways utilized to construct this privileged scaffold and structure activity relationship that accounts for the anti-inflammatory activity in an attempt to pave the opportunity for medicinal chemists to develop novel anti-inflammatory agents with better COX-2 selectivity., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In order to develop novel antimicrobial agents, we prepared quinoline bearing pyrimidine analogues 2-7, 8 a-d and 9 a-d and their structures were elucidated by spectroscopic techniques. Furthermore, our second aim was to predict the interactions between the active compounds and enzymes (DNA gyrase and DHFR). In this work, fourteen pyrimido[4,5-b]quinoline derivatives were prepared and assessed for their antimicrobial potential by estimating zone of inhibition. All the screened candidates displayed antibacterial potential with zone of inhibition range of 9-24 mm compared with ampicillin (20-25 mm) as a reference drug. Moreover, the target derivatives 2 (ZI=16), 9 c (ZI=17 mm) and 9 d (ZI=16 mm) recorded higher antifungal activity against C. albicans to that exhibited by the antifungal drug amphotericin B (ZI=15 mm). Finally, the most potent pyrimidoquinoline compounds (2, 3, 8 c, 8 d, 9 c and 9 d) were docked inside DHFR and DNA gyrase active sites and they recorded excellent fitting within the active regions of DNA gyrase and DHFR. These outcomes revealed us that compounds (2, 3, 8 c, 8 d, 9 c and 9 d) could be lead compounds to discover novel antibacterial candidates., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A series of spiro β-Lactams (4 a-c, 7 a-c) and thiazolidinones (5 a-c, 8 a-c) possessing 1,8-naphthyridine moiety were synthesized in this study. The structure of the newly synthesized compounds has been confirmed by IR, 1 H-NMR, 13 C NMR, mass spectra, and elemental analysis. The synthesized compounds were tested in vitro for their antibacterial and antifungal activity against various strains. The antimicrobial data showed that most of the compounds displayed good efficacy against both bacteria and fungi. The structure-activity relationship (SAR) studies suggested that the presence of electron-withdrawing chloro (3 b, 4 b, and 5 b) and nitro groups (7 b, 8 b) at the para position of the phenyl ring improved the antimicrobial activity of the compounds. The free radical scavenging assay showed that all the synthesized compounds exhibited significant antioxidant activity on DPPH. Compounds 8 b (IC 50 =17.68±0.76 μg/mL) and 4 c (IC 50 =18.53±0.52 μg/mL) showed the highest antioxidant activity compared to ascorbic acid (IC 50 =15.16±0.43 μg/mL). Molecular docking studies were also conducted to support the antimicrobial and SAR results., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Clozapine (CLZ), a second-generation antipsychotic, can effectively reduce schizophrenia, bipolar disorder and major depression symptoms. This review provides an overview of all reported chromatographic methods (62 references) for the quantification of CLZ and its two main metabolites, norclozapine and clozapine N-oxide in pharmaceutical formulations, biological matrices and environmental samples., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Among the toxic heavy metals, Ni(II) can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung, and nasal cancer. It is therefore critical from a public health and environmental perspective to determine and monitor Ni(II) ions in drinking water, foods, and environmental samples. In this study, a novel selective chemosensor (4-[{[4-(3-Chlorophenyl)-1,3-Thiazol-2-yl]Hydrazono}Methyl]phenyl4-methylBenzene Sulfonate (CTHMBS) was developed for the colorimetric detection of Ni(II) in aqueous medium. The presence of Ni(II) led to a distinct naked-eye color change from yellow to reddish-brown in aqueous solution. To examine the binding mechanism of CTHMBS to Ni(II), UV-vis spectroscopy analysis and DFT calculations were conducted. The detection limit of CTHMBS for Ni(II) was 11.87 µM, and the sensing ability of CTHMBS for Ni(II) was successfully carried out in real water samples., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Unintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4-acetylphenyl 4-methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1 H-NMR, 13 C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4-[3-(4-Methylphenyl)prop-2-enoyl]phenyl-4-methyl benzenesulfonate (4) was the most active with an LC 50 =3.46 mg/L of 2 nd instar larvae and LC 50 =9.45 mg/L of 4 th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes.Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs.Novel pyridopyrimidines, 9a-j, were prepared and their chemical structures were confirmed by NMR, mass and IR Spectra, and elemental analysis. The effect of the 9a-j compounds on COX-1 and COX-2 was assessed and it was found that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3 H -pyrido[2,3- d )pyrimidin-4-one ( 9d ) was the most potent COX-2 inhibitor (IC 50 = 0.54 u M) compared to celecoxib (IC 50 = 1.11 u M) with selectivity indices of 6.56 and 5.12, respectively.The in vivo inhibition of paw edema of novel compounds 9a-j was measured using carrageenan-induced paw edema method, and that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3 H -pyrido[2,3- d )pyrimidin-4-one ( 9d ) showed the best inhibitory activity in comparison with the other compounds and celecoxib.The gastroprotective effect of the potent derivatives 9d, 9e, 9f, 9 g and 9h was investigated. 2-Hydrazino-5-(4-methoxyphenyl)-7-phenyl-3 H -pyrido[2,3- d )pyrimidin-4-one ( 9d ) and 7-(chlorophenyl)-hydrazino-5-(4-methoxyphenyl)-3 H -pyrido[2,3- d )pyrimidin-4-one ( 9e ) showed ulcer indices comparable to celecoxib (1 and 0.5 vs 0.5, respectively). Docking studies were carried out and they confirmed the mechanistic action of the designed compoundsCommunicated by Ramaswamy H. Sarma.

Treatment of p-tosyloxybenzaldehyde (1) with ethyl cyanoacetate afforded ethyl 2-cyano-3-(4-{[(4-methylphenyl)sulfonyl]oxy}phenyl)acrylate (2) which reacted with some active methylene derivatives under microwave irradiation in presence of ammonium acetate yielded pyridine derivatives 3-7. On the other hand, when treatment of compound 1 with thiosemicarbazide gave 4-tosyloxybenzylidenethiosemicarbazone (8), which allowed to react with some active methylene compounds, such as: ethyl bromoacetate, chloroacetonitrile or phenacyl bromide derivatives gave thiazole derivatives 9-13. The structure of all products were confirmed by elemental and spectroscopic analyses such as IR, 1 H-NMR, 13 CNMR and mass spectra. The advanced of this method are short reaction time (3-7 min), excellent yield, pure products, and low-cost processing. In the final category, the toxicological characteristics of all compounds were tested towards Saissetia oleae (Olivier, 1791) (Hemiptera: Coccidae). With respect to the LC 50 values. It has been found that compound 3 possesses the highest insecticidal bioefficacy compared with other products, with values of 0.502 and 1.009 ppm, for nymphs and adults female, respectively. This study paves the way towards discovering new materials for potential use as insecticidal active agents., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

A functional and environmentally green procedure for the design of novel pyridine 5a - h and 7a - d derivatives through two pathways is presented. The first pathway is via a one-pot, four-component reaction of p -formylphenyl-4-toluenesulfonate ( 1 ), ethyl cyanoacetate ( 2 ), acetophenone derivatives 3a-h or acetyl derivatives 6a - d , and ammonium acetate ( 4 ) under microwave irradiation in ethanol. The advantages of this method are an excellent yield (82%-94%), pure products, a short reaction time (2-7 min), and low-cost processing. The second pathway was obtained by the traditional method with treatment of the same mixture under refluxing in ethanol, which afforded the same products, 5a - h and 7a - d , in less yield (71%-88%) and over a longer reaction time (6-9 h). The constructions of the novel compounds were articulated via spectral and elemental analysis. Overall, the compounds have been designed, synthesized, and studied for their in vitro anti-inflammatory activity using diclofenac as a reference drug (5 mg/kg). The most potent four compounds, 5a , 5f , 5g , and 5h , showed promising anti-inflammatory activity., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Spodoptera frugiperda is a species of the order Lepidoptera. It is one of the species of fall armyworm moths distinguished by its larval life stage, is found in different regions of Africa, and can cause incredible damage. This is the first report produced by the preparation of an indexed combinatorial library of novel chalcone derivatives 3a-k via treatment of 4-formylphenyl4-methylbenzenesulfonate ( 1 ) with some acetyl compounds 2a-k in the presence of NaOH. The structures of the synthesized compounds were proven by different spectroscopic techniques such as infrared, 1 H NMR, 13 C NMR, and elemental analyses. In this work, we studied their toxicity effect against S. frugiperda , followed by a structure-reaction relationship. Moreover, newly prepared chalcone derivatives were tested as insecticides using S. frugiperda . It has been found that most compounds have good to excellent potential effectiveness. Among all of the compounds, 3b , 3g , and 3j exhibited excellent effectiveness. Furthermore, compound 3c showed the most activity, with LC 50 = 9.453 ppm of the second instar larva and LC 50 = 66.930 of the fourth instar larva ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In this study, pumice is used as a novel natural heterogeneous catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1 H )-ones/thiones via the one-pot multi-component condensation of aromatic aldehydes, urea/thiourea, and ethyl acetoacetate or acetylacetone in excellent yields (up to 98%). The physical and chemical properties of the catalyst were studied. Their geochemical analysis revealed a basaltic composition. Furthermore, X-ray diffraction showed that it is composed of amorphous materials with clinoptilolite and heulandites zeolite minerals in its pores. Moreover, pumice has a porosity range from 78.2-83.9% (by volume) and is characterized by a mesoporous structure (pore size range from 21.1 to 64.5 nm). Additionally, it has a pore volume between 0.00531 and 0.00781 m 2 /g and a surface area between 0.053 and 1.47 m 2 /g. The latter facilitated the reaction to proceed in a short time frame as well as in excellent yields. It is worth noting that our strategy tolerates the use of readily available, cheap, non-toxic, and thermally stable pumice catalyst. The reactions proceeded smoothly under solvent-free conditions, and products were isolated without tedious workup procedures in good yields and high purity. Indeed, pumice can be reused for at least five reuse cycles without affecting its activity.

Chalcone derivatives are considered valuable species because they possess a ketoethylenic moiety, CO-CH=CH-. Due to the presence of a reactive α,β-unsaturated carbonyl group, chalcones and their derivatives possess a wide spectrum of antiproliferative, antifungal, antibacterial, antiviral, antileishmanial, and antimalarial pharmacological properties. Recent developments in heterocyclic chemistry have led to the synthesis of chalcone derivatives, which had been biologically investigated toward certain disease targets. The major aspect of this review is to present the most recent synthesis of chalcones bearing N, O, and/or S heterocycles, revealing their biological potential during the past decade (2010-2021). Based on a review of the literature, many chalcone-heterocycle hybrids appear to exhibit promise as future drug candidates owing to their similar or superior activities compared to those of the standards. Thus, this review may prove to be beneficial for the development and design of new potent therapeutic drugs based on previously developed strategies., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

An efficient and environmentally friendly method was established for designing novel 3-amino-1,4-dihydroquinoxaline-2-carbonitrile ( 1 ) via the reaction of bromomalononitrile and benzene-1,2-diamine under microwave irradiation in an excellent yield (93%). This targeted amino derivative was utilized for the construction of a series of Schiff bases ( 8 - 13 ). A new series of thiazolidinone derivatives ( 15 - 20 ) were synthesized in high yields (89-96%) via treatment of thioglycolic acid with Schiff bases ( 8 - 13 ) under microwave irradiation in high yields (89-96%). Moreover, new pyrimidine derivatives ( 26 - 30 and 35 - 38 ) were prepared by treatment of compound 1 with arylidenes ( 21 - 25 ) and/or alkylidenemalononitriles ( 31 - 34 ) using piperidine as a basic catalyst under microwave conditions. Based on elemental analyses and spectral data, the structures of the new assembled compounds were determined. The newly synthesized quinoxaline derivatives were screened and studied as an insecticidal agent against Aphis craccivora . The obtained results indicate that compound 16 is the most toxicological agent against nymphs of cowpea aphids ( Aphis craccivora ) compared to the other synthesized pyrimidine and thiazolidinone derivatives. The molecular docking study of the new quinoxaline derivatives registered that compound 16 had the highest binding score (-10.54 kcal/mol) and the thiazolidinone moiety formed hydrogen bonds with Trp143., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

An eco-friendly green bio-organic catalyst and low-cost 3,4-dihydropyrimidin-2(1 H )-ones/thione derivatives 4-7 have been synthesized using a high-yield, synthetic method via a one-pot, three-component process between 4-formylphenyl-4-methylbenzenesulfonate ( 1 ), thiourea, or urea and ethyl acetoacetate or acetylacetone under microwave irradiation in aqueous media of water and ethanol (3:1 ratio) as a green solvent in the presence of cysteine as a new green bio-organic catalyst. The reaction between compound 1 , 4-(carbamothioylhydrazono) methyl]phenyl 4-methyl benzenesulfonate ( 3c ), and ethyl acetoacetate or acetylacetone under the same condition afforded novel pyrimidines. Similarly, compound 1 was allowed to react with a mixture of 4-(carbamothioylhydrazono)methyl]phenyl 4-methyl benzenesulfonate ( 3c ) and ethyl acetoacetate or acetylacetone under the same condition to afford pyrimidine derivatives 8 and 9 . Excellent yields (90-98%) were obtained within short reaction times, and problems associated with the toxic solvents used (cost, safety, and pollution) were avoided. The structures of the new compounds were elucidated by elemental and spectral analyses. All compounds were studied using molecular docking, and their antifungal activity was investigated., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4 , via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates ( 5 - 16 ). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5 - 13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC 50 = 17.50-61.05 µM, especially the naphthyridine derivative 7 , which exhibited the most cytotoxic potential towards the tested cell lines (IC 50 = 14.62-17.50 µM) compared with the etoposide (IC50 = 13.34-17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were in vitro estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC 50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC 50 = 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies 7 , 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

In search of unprecedented tri and/or tetrapod pharmacophoric conjugates, a series of 32 new 4-ethyl-1 H -benzo[ b ][1,4]diazepin-2(3 H )-ones were synthesized and properly elucidated using MS, IR, NMR, and elemental analysis. In vitro investigation of 11 compounds of this series, using a panel of two human tumor cell lines namely; human breast adenocarcinoma (MCF-7), and human colorectal carcinoma (HCT-116), revealed promising cytotoxic activities. Among all synthesized compounds, analogue 9 displayed maximum cytotoxicity with IC 50 values of 16.19 ± 1.35 and 17.16 ± 1.54 μM against HCT-116 and MCF-7, respectively, compared to standard drug doxorubicin.

A series of 34 new pyrimido[2,1- c ][1,2,4]triazine-3,4-diones were synthesized and fully characterized using IR, NMR, MS, and microanalytical analysis. In vitro investigation of 12 compounds of this series revealed promising antimicrobial activity of the conjugates 15a and 15f - j that were tagged with electron-withdrawing groups, with sensitivities ranging from 77% to as high as 100% of the positive control. The investigation of antimicrobial activity included Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6535, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 8739 (EC), and fungal strains Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404.