Pharmacophore modeling in drug design

Maji, Siddhartha; Pattanayak, Subrat Kumar; Sen, Anik; Badavath, Vishnu Nayak

doi:10.1016/b978-0-323-90608-1.00002-2

Cited by 2 publications

(2 citation statements)

References 92 publications

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“…The pharmacophore model was obtained through the alignment of the molecular structures of the ten FDA-approved active compounds against COVID-19, which comprise the training set. The alignment revealed a favorable fit [ 68 , 69 ], as depicted in Supplementary Information Figure S38. The pharmacophore model was composed of three indispensable characteristics: Feature F1 exhibits hydrophobic properties due to its chemical structure, characterized by the presence of hydrophobic groups.…”

Section: Resultsmentioning

confidence: 99%

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

El-Saghier,

Enaili,

Abdou

et al. 2023

Mol Divers

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Introduction The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed. Problem statement The SARS-CoV-2 main protease (Mpro) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of Mpro enzyme can be an effective strategy for developing new COVID-19 drugs. Methodology An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski’s rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (Mpro) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis. Findings The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from − 7.33 kcal/mol (compound 6) and − 7.22kcal/mol (compound 5) to − 6.54 kcal/mol (compounds 8 and 9). The top-ranked compounds (5 and 6) had lower HOMO–LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level. Recommendation These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

El-Saghier,

Enaili,

Abdou

et al. 2023

Mol Divers

View full text Add to dashboard Cite

show abstract

“…The pharmacophore model was developed by aligning the structures of the ten approved FDA active compounds against COVID-19 (training set), which were very well aligned and are present in Supplementary Information, Figures S1 and S2 [45,46]. Supplementary Information, Figure S3, shows the pharmacophore model derived thereof.…”

Section: Pharmacophore Analysismentioning

confidence: 99%

Synthesis and in Silico Investigation of Organoselenium-Clubbed Schiff Bases as Potential Mpro Inhibitors for the SARS-CoV-2 Replication

Shaaban

Abdou

Alhamzani

et al. 2023

Life

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Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6–311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from −8.19 to −7.33 Kcal/mol for 4c and 4a to −6.10 to −6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good Mpro inhibitors. Moreover, the drug-likeness studies, including Lipinski’s rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.

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Pharmacophore modeling in drug design

Cited by 2 publications

References 92 publications

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

Synthesis and in Silico Investigation of Organoselenium-Clubbed Schiff Bases as Potential Mpro Inhibitors for the SARS-CoV-2 Replication

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