Synthesis of 4-(3-(1-substituted/unsubstituted-phenyl-1H-1,2,3-triazole-4-yl)propoxy)benzaldehydes: In vitro antimicrobial, antimalarial activities and In silico docking study

In this work, we have developed new derivatives of 4-(3-(1-substituted/unsubstituted phenyl-1H-1,2,3-triazol-4-yl)propoxy)benzaldehydes 3(a-o) in good to excellent yield through the click reaction catalyzed by Copper(II) sulfate pentahydrate. 5-chloropent-1‑yne was used as an alkynylation reagent for 4-hydroxybenzaldehyde, whereas the aromatic azides were prepared from the corresponding diazonium salt by diazotization. All the newly synthesized derivatives were well characterized by FT-IR, 1H/ 13C NMR, high-resolution mass spectrometry and elemental analyses. These compounds were evaluated for their in vitro anti-microbial against six pathogenic strains as well as two pathogenic strains as anti-fungal activities using the broth dilution method. The activity results show that most of the compounds exhibit moderate to very good antibacterial and antifungal activities compared to the reference drugs. Furthermore, the in vitro antimalarial assay of synthesized compounds was screened against P. falciparum strain and then compared to Quinine and Chloroquine as the reference drugs. The results from the activity evaluation revealed that three out of fifteen compounds presented moderate efficacy when compared to Quinine. The structure-activity relationship (SAR) study indicated that substituted compounds with deactivating groups have potent antibacterial, antifungal, and antimalarial activities. Moreover, in silico molecular docking assay shows that 3 m is the most potent amongst 3(a-o) with a binding energy of -8.1 kcal/mol and -8.9 kcal/mol in the binding pocket of the receptor for bacterial and fungal infections, respectively compared to the standard drugs. The molecule 3 m has been studied in details for its ADMET properties and showed the most promise as a drug candidate.