Synthesis of New Bisphosphonate and Bisphosphonic Acid Derivatives and Heterocyclic and Dialkylcarbamoyl Oxazolone Derivatives with Anticancer and Antischistosomal Activity

Boulos, L. S.; Ewies, Ewies F.; Fahmy, A. F. M.

doi:10.1515/znb-2011-1011

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…Based on the above, a number of new benzamides was designed guided by quantitative structure activity relationship (QSAR) results [ 23 ] and synthesized from appropriate substituted 5-(4 H )-oxazolones. Benzamides A ( Figure 2 ) are biologically active agents demonstrating antibacterial, antiproteolytic-antiviral, antischistosomal and anti-inflammatory activities [ 24 , 25 , 26 , 27 ]. On the other hand 5-(4 H )-oxazolones B show a variety of biological activities: analgesic, antimicrobial, antidiabetic, anti-inflammatory as well as inhibition of trypsin and tyrosinase [ 28 , 29 , 30 ] ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

5-(4H)-Oxazolones and Their Benzamides as Potential Bioactive Small Molecules

et al. 2020

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The five membered heterocyclic oxazole group plays an important role in drug discovery. Oxazolones present a wide range of biological activities. In this article the synthesis of 4-substituted-2-phenyloxazol-5(4H)-ones from the appropriate substituted aldehydes via an Erlenmeyer–Plochl reaction is reported. Subsequently, the corresponding benzamides were produced via a nucleophilic attack of a secondary amine on the oxazolone ring applying microwave irradiation. The compounds are obtained in good yields up to 94% and their structures were confirmed using IR, 1H-NMR, 13C-NMR and LC/MS data. The in vitro anti-lipid peroxidation activity and inhibitory activity against lipoxygenase and trypsin induced proteolysis of the novel derivatives were studied. Inhibition of carrageenin-induced paw edema (CPE) and nociception was also determined for compounds 4a and 4c. Oxazolones 2a and 2c strongly inhibit lipid peroxidation, followed by oxazolones 2b and 2d with an average inhibition of 86.5%. The most potent lipoxygenase inhibitor was the bisbenzamide derivative 4c, with IC50 41 μM. The benzamides 3c, 4a–4e and 5c were strong inhibitors of proteolysis. The replacement of the thienyl moiety by a phenyl group does not favor the protection. Compound 4c inhibited nociception higher than 4a. The replacement of thienyl groups by phenyl ring led to reduced biological activity. Docking studies of the most potent LOX inhibitor highlight interactions through allosteric mechanism. All the potent derivatives present good oral bioavailability.

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Section: Introductionmentioning

confidence: 99%

5-(4H)-Oxazolones and Their Benzamides as Potential Bioactive Small Molecules

et al. 2020

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“…Due to the various applications of hexamethyl phosphorus triamide in industrial, biological, and pharmacological activities, it is a synthetic target of interest. However, tris (dimethylamino)phosphine ( 13) is a strong nucleophile [51] used to synthesize epoxides and arene oxides from aldehydes [52][53][54]. Moreover, it replaces triphenylphosphane in the Wittig reaction for the preparation of unsaturated esters as well as alkenes [55] and provides convenient synthetic access to epoxides [55,56].…”

Section: Chemistrymentioning

confidence: 99%

The synthesis and antineoplastic activities of thiaziridine, sulfidometylphosphonium, and dithiaphosphitane‐sulfide against the Ehrlich ascites carcinoma

Mansour

Hashem

Abd‐El‐Maksoud

et al. 2022

Fundamemntal Clinical Pharma

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Phosphonium compounds offer an attractive branch of research that chemists and biologists apply for producing many novel drugs for various applications, and its polymeric ingredients are composed of quaternary ammonium and phosphonium salts. The reactions of isothiocyanate with phosphinimine bestow thiaziridine, carbamate, and thiourea derivatives. Moreover, isothiocyanate reacts with tris (dimethylamino) phosphine leading to the formation of sulfidomethyl phosphonium. Lawesson's and Japanese reagents have potential to react with isothiocyanates to generate dithiaphosphetane sulfides. Treatment of isocyanate with Lawesson's or Japanese reagents under reflux conditions affords thiaphosphetidinone sulfide, but when applied at room temperature, the dithiaphosphetane sulfide was isolated. Ehrlich ascites carcinoma (EAC) mice model was used to investigate potential anticancer properties of the novel phosphonium and thiophosphate derivatives. Synthesized compounds (100 mg/kg b.w.) were administered orally to the EAC‐bearing mice for about 2 weeks. Compounds' antineoplastic activity was determined by the evaluation of volume, viability, and inhibition percent of EAC cells. In addition, DNA fragmentation percent was assessed. The expression of apoptotic marker genes (Bax, Bcl2, Caspase 3) and encoding proinflammatory cytokines (TNF‐α) and pro‐apoptotic protein (p53) were inspected by real time‐quantitative polymerase chain reaction (RT‐qPCR). The overall conclusion was based on the findings that treatment with synthesized compounds leads to decrease in tumor volume, increase in tissue DNA fragmentation, downregulation of Bcl2 gene, and upregulation of Bax, caspase3, and p53 markers, along with decrease in TNF‐α level in liver tissues. These findings suggest that the anticancer mechanism of these compounds is based on the programmed cell death (Apoptosis).

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“…Moreover, azides are important building blocks due to their potential application in organic and bioorganic chemical reactions . In the light of this survey and our interest in synthesis of heterocyclic chemistry, we have now studied the reactivity of azidopyrazole carbaldehyde 1 towards certain active methylenes ( 2a‐e , 3 ), primary amines ( 4a‐g ), and hydrazines ( 4h‐k ) aiming at preparing new heterocycles of anticipated anticancer and antimicrobial activities (Figure ).…”

Section: Introductionmentioning

confidence: 99%