Probing the Action of Screened Anticancer Triazole–Tetrazole Derivatives Against COVID-19 Using Molecular Docking and DFT Investigations

Abstract

Drugs are continuously being evaluated for novel therapeutic uses. The purpose of this work was to screen anticancer triazole/tetrazole derivatives for effectiveness against the SARS-CoV-2 main protease (Mpro). First, the chemical structures’ activity was derived from conceptual quantum chemical calculations. According to molecular docking analysis, the compounds scored good interactions against SAR-COV-2's Mpro, with binding energies extending from −8.21 to −8.97 kcal/mol. The docked complexes included various bindings with His41 and Cys145, both catalytic residues responsible for cleavage of the SARS-CoV-2 Mpro. Among the 4 studied compounds, TD3 exhibited the highest affinity by achieving the most stable binding energy and lowest value for the inhibition constant. Most striking was that TD3 not only formed strong bonds with the catalytic residues His41 and Cys145, but also captured the residues of the catalytic loop (Cys44 to Pro52), which flank the catalytic dyads in Mpro's active site. As a result, the studied triazole/tetrazole derivatives, notably TD3, must be reviewed as potent drugs that could be repurposed for SARS-CoV-2 treatment.

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2

“…As sterols interact with the active site, they can be promising candidates, particularly oxygenous tetrahydroxy sterol, which has a high tendency to form hydrogen bonds. Schiff base ligands have been shown to inhibit M pro in previous studies [ 54 ] as well as caffeine [ 54 , 55 ], nethylxanthines [ 56 ], natural product isolates [ 57 ], glycyrrhizin [ 58 ], ML188 [ 59 ], pyrimidonic and pyridonic pharmaceuticals [ 60 , 61 ], kaempferol [ 62 ], fungal natural products [ 63 ], marine natural compounds [ 64 ], Ceftazidime [ 65 ], hepatitis C virus protease drugs [ 66 ], and other inhibitors [ 67 , 68 , 69 , 70 , 71 , 72 ]. In our molecular docking study, these natural compounds were identified as potential M pro inhibitors.…”

Synthesis and Catalytic Application of MTsCOO‐Cu as a Melamine‐Based Metal‐Organic Framework in Facile Preparation of the 5‐Substituted‐1H‐Tetrazoles

“…Against COVID-19 [27] 5 Antimicrobial [28] 6 Anticancer The progress of the reaction was monitored by TLC (nhexane/EtOAc, 4 : 1, V/V). After completion of reaction, monitored with TLC, the reaction mixture was cooled to room temperature.…”

“…Actually, many important chem-ical compounds bearing tetrazole rings have shown effective clinical properties, such as antibacterial, antifungal, antidiabetic, anticancer, anti-inflammatory, anti-asthmatic, anti-HIV, analgesic, etc. [25,26] Recently, massive efforts are devoted to design and develop new medicinal compounds based on triazole and tetrazole moieties for the treatment of the new class of pandemic, such as SARS-CoV-2 and COVID-19 [27] (Table 1).…”