New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

Seliem, Israa A.; Girgis, Adel S.; Moatasim, Yassmin; Kandeil, Ahmed; Mostafa, Ahmed; Ali, Mohamed A.; Bekheit, Mohamed S.; Panda, Siva S.

doi:10.1002/cmdc.202100476

Cited by 23 publications

(17 citation statements)

References 41 publications

(79 reference statements)

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“…The synthesized conjugates 7 a–k were subjected to antiviral properties against SARS‐CoV‐2 utilizing the standard technique [73] . From the observed results (Table 5, Figure 8) it is noticeable that all the synthesized conjugates are with higher efficacies than that of the standard reference used (favipiravir).…”

Section: Resultsmentioning

confidence: 98%

“…From the observed results (Table 5, Figure 8) it is noticeable that all the synthesized conjugates are with higher efficacies than that of the standard reference used (favipiravir). Considering that favipiravir is clinically approved under the emergency use authorization for fighting the global pandemic of COVID‐19 [73,74] . Compound 7 f (IC 50 =10.1 μ M) is the most effective conjugate synthesized.…”

Section: Resultsmentioning

confidence: 99%

“…Considering that favipiravir is clinically approved under the emergency use authorization for fighting the global pandemic of COVID-19. [73,74]…”

Section: Antiviral Propertiesmentioning

confidence: 99%

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Novel Curcumin Mimics: Design, Synthesis, Biological Properties and Computational Studies of Piperidone‐Piperazine Conjugates

et al. 2022

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alkyl]piperidin-4-ones 7 aÀ k were synthesized through dehydrohalogenation of 1-(2-chloroacyl)piperidin-4-ones 5 aÀ k with N-methylpiperazine (6). High antiproliferation potencies were observed by most of the synthesized agents against both HCT116 (colon) and MCF7 (breast) cancer cell lines relative to the standard references (sunitinib and 5-fluorouracil). The synthesized agents are of dual activity against topoisomerases I and IIα however, with higher efficacy against topoisomerase IIα rather than topoisomerase I. Flow-cytometry cell cycle studies support the observed antiproliferation properties and exhibit the capability of 1-(2-chloroacetyl)-3,5-bis[(E)-4-chlorobenzylidene]piperidin-4-one (5 e) and 3,5-bis[(E)-4-bromobenzylidene]-1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-one (7 g) to arrest the HCT116 cell cycle progression at G1/S and G1 phases, respectively. Noticeable anti-SARS-CoV-2 properties were observed by many synthesized agents. 3,5-Bis[(E)-4-chlorobenzylidene]-1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-one (7 f) is the most effective anti-SARS-CoV-2 synthesized with high SI. Applicability of the highly effective candidates synthesized as antitumor and anti-SARS-CoV-2 is due to the safety observations against normal (RPE1 and VERO-E6) cells. QSAR models validated internally and externally, support their possibility for optimizing more hits/leads.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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Novel Curcumin Mimics: Design, Synthesis, Biological Properties and Computational Studies of Piperidone‐Piperazine Conjugates

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“…The Vero-E6 cell viral infection model/technique was undertaken to determine the anti-SARS-CoV-2 inhibitory properties of the synthesized spiro-3-indolin-2-ones 6a‒o 44 . Favipiravir 89 , Hydroxychloroquine and Chloroquine 51 were considered as standard references (Table 5 , Fig. 9 ).…”

Section: Resultsmentioning

confidence: 99%

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

Fawazy

Panda

Mostafa

et al. 2022

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A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2′-pyrrolidine-3′,3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties.

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“…There were attempts to synthesize new analogs of 2-pyrazinecarboxamide to enhance antiviral activity against SARS-CoV-2 [ 72 ]. A series of seven pyrazine- triazole ( 16 ) and 11 pyrazine-benzothiazole ( 17 ) heterocyclic bases was synthesized.…”

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

et al. 2022

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1,4-Pyrazine-3-carboxamide-based antiviral compounds have been under intensive study for the last 20 years. One of these compounds, favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705), is approved for use against the influenza infection in a number of countries. Now, favipiravir is being actively used against COVID-19. This review describes the in vivo metabolism of favipiravir, the mechanism of its antiviral activity, clinical findings, toxic properties, and the chemical synthesis routes for its production. We provide data on the synthesis and antiviral activity of structural analogs of favipiravir, including nucleosides and nucleotides based on them.

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New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

Cited by 23 publications

References 41 publications

Novel Curcumin Mimics: Design, Synthesis, Biological Properties and Computational Studies of Piperidone‐Piperazine Conjugates

Novel Curcumin Mimics: Design, Synthesis, Biological Properties and Computational Studies of Piperidone‐Piperazine Conjugates

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

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