Supramolecular Microtubes by Self‐Assembly of a Co–Drug and Antifungal Activities against Saccharomyces cerevisiae

Abstract

Benzotriazole esters have been reported to work as inactivators for severe acute respiratory syndrome (SARS) 3CL protease. A calcium channel blocker m‐Nifedipine is well known for its effect in hypertension, as well as angina. Combining two, we have synthesized co‐drug m‐Nifedipine‐3‐benzotriazol‐1‐yl‐ester 1 which exhibited antifungal activities against Saccharomyces cerevisiae (S. cerevisiae strain BY4742). The single‐crystal X‐ray diffraction study shows that there are two molecules with opposite chirality in the asymmetric unit. Intramolecular π‐π stacking interactions stabilize the tripod shape compound 1 molecules. In higher‐order assembly, compound 1 molecules are assembled by intermolecular hydrogen bonding, maintaining a proper registry to form a supramolecular nanotube‐like structure. Moreover, compound 1 inhibits the growth of the Saccharomyces cerevisiae. The minimal inhibitory concentration (MIC) against the Saccharomyces cerevisiae was 10 μg/mL. The docking studies indicate that compound 1 has a strong affinity (binding energy −8.67 kcal/mol) for the enzyme lanosterol 14α‐demethylase of the Saccharomyces cerevisiae. The compound 1 binds to Leu58 and Ser50 of lanosterol 14α‐demethylase through intermolecular hydrogen bonding interactions.

Synthesis and Structural Investigation of Foldamer‐Based Iodine‐Supported Artificial Glycosidases

“…[17] We have also shown the antifungal activities of m-Nifedipine derivative against Saccharomyces cerevisiae. [18] Given intriguing and compelling information from previous reports, we have designed and synthesized an enzyme mimetic containing l-phenylalanine, α-aminoisobutyric acid (Aib), l-leucine, and m-Nifedipine. From X-ray crystallography results, the peptide adopts a β-hairpin conformation that is stabilized by two 10-member and one 18-member NH•••O=C hydrogen bonds.…”

“…Recently, we investigated and reported the impact of spatial folding of molecules on two‐photon absorption and nonlinear refraction in foldamers [17] . We have also shown the antifungal activities of m‐Nifedipine derivative against Saccharomyces cerevisiae [18] . Given intriguing and compelling information from previous reports, we have designed and synthesized an enzyme mimetic containing l ‐phenylalanine, α‐aminoisobutyric acid (Aib), l ‐leucine, and m ‐Nifedipine.…”