Rigidity and Flexibility of Pyrazole, s-Triazole, and v-Triazole Derivative of Chloroquine as Potential Therapeutic against COVID-۱۹

Based on the core unit of chloroquine, new types of N-heterocyclic compounds that are fused together have been made. The compounds were put into two groups. In series A, the five-member hetero-rings were directly connected to the core unit, while in series B, the CH۲ group was used to make the five-member ring more flexible (series B). Using the Gaussian ۰۹ programme, the DFT method with hybrid correlation functional (B۳LYP) and ۶-۳۱۱ (d, p) basis sets were used to figure out how to optimize and measure the quantum chemical properties of molecules. The molecular overeating environment (MOE) programme is used to study molecular docking. The binding of flexible compounds shows that AC۸, AC۱۰, AC۳, and AC۵ have the strongest binding affinities compared to the other candidates, while the rigid molecules ARC۱۰ and ARC۶ have the lowest binding affinities. In general, the results of the binding affinity showed that the drugs and receptors being studied might have anti-Covid-۱۹ properties. Likewise, the flexible compounds AC۸, AC۱۰, AC۳, and AC۵ had the lowest Ki values of those made and could be used as a treatment. Our virtual physicochemical evaluation of all compounds in series A and B showed that all of them met the limits for molecular weight, lipophilicity (MLogP ۴.۱۵, the octanol-water partition coefficient), and water solubility. In addition to MR, the number of H-bond acceptors and the PSA were both within the acceptable range. It seems that the number of rotatable bonds is the only physicochemical property that separates the compounds in series B. The scores of compounds AC۳, AC۴, AC۷, AC۸, AC۱۱, and AC۱۲ are outside the acceptable range when compared to the results of chloroquine as the parent compound.

Keywords:

COVID-۱۹ Pryazole ۱ , ۴-Triazole ۱ , ۲ , ۳-Triazole Hydroxychloroquine DFT Molecular Docking Drugs design