A variety of novel 2-(substituted)-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamides were synthesized by the reaction of 2-chloro-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamide with various amines. The starting material, 2-chloro-N-(4-oxo-2-phenylquinazolin-3(3H)-yl) acetamide, was synthesized from anthranilic acid by the multistep process. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. Among those, the compound 2-(ethylamino)-N-(4-oxo-2-phenylquinazolin-3(3H)-yl) acetamide (V9) showed most potent analgesic and antiinflammatory activities of the series and it is moderately more potent compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential compared to aspirin.
Background:
Severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) is an important target for drug development amidst whole variants of coronaviruses, a vital protein for the replication cycle of virus.
Objective:
The main aim of this study is to discover and recognize the most effective and promising molecules against Mpro enzyme through molecular docking screening of 120 phytochemicals from six different Ayurveda medicinal plants.
Methods:
The phytochemicals were downloaded from PubChem, and SARS-CoV-2 Mpro was taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed.
Results:
Molecular docking analysis identified 10 phytochemicals, castalagin (-10.4 kcal/mol), wedelolactone (-8.0 kcal/mol), arjungenin (-7.7 kcal/mol), betulin (-7.7 kcal/mol), galbacin (-7.6 kcal/mol), shinpterocarpin (-7.6 kcal/mol), liquirtin (-7.4 kcal/mol), cordioside (-7.3 kcal/mol), licopyranocoumarin (-7.3 kcal/mol), and daucosterol (-7.1 kcal/mol) from different kinds of ayurvedic medicinal plants’ phytochemicals possessing greater affinity against Mpro of SARS-CoV-2. Two molecules, namely castalagin and wedelolactone, with low binding energies were the most promising. Furthermore, we carried out MD simulations for the castalagin complexes based on the docking score.
Conclusion:
Molecular ADMET profile estimation showed the docked phytochemicals to be safe. The present study suggested that active phytochemicals from medicinal plants could inhibit Mpro of SARS-CoV-2.
Background:
To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses.
Objective:
This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants.
Methods:
The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed.
Results:
Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphnol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes.
Conclusion:
Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.
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