Biological Evaluation of Pillar[5]arene-Isatin Inclusion Complexes to Combat Wound Infections
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Date
2025-01
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Avinashilingam
Abstract
Wound infections have become a serious threat at the global level due to biofilm forming bacterial pathogens. There is a need for the development of alternative strategies to prevent complications of drug resistance. Natural compounds have been a prime choice for microbial treatment but have a poor pharmacokinetic profile. To circumvent these challenges, a suitable drug delivery system is of paramount importance, utilizing the host-guest complexation to protect the drug from premature degradation and deactivation. Hence, the current study was designed to explore the host-guest inclusion complexes for the prevention and treatment of wound infections. Isatin, an alkaloid isolated from the Couroupita
guianensis Aubl. flower, was selected as the drug molecule owing to its traditional use in treating various infections. Likewise, pillar[5]arenes (P[5]A) and bis-ethanolamine functionalized pillar[4]arene[1]quinine (BEA) were selected as supramolecular hosts to capture isatin into their electron-rich cavities to reinforce the controlled release and targeted activity. The pharmacokinetic profiles of the selected hosts revealed their potential druggable nature. The synthesized P[5]A and BEA were characterized by proton NMR and UV-visible spectroscopy which revealed that P[5]A exhibited a superior capacity to encapsulate isatin in comparison with BEA. Job’s plot analysis validated the 1:1 binding stoichiometry between P[5]A and isatin, highlighting the specificity and stability of the formed complexes. Further, the synthesized P[5]A-isatin inclusion complexes showed enhanced antibacterial properties and exhibited strong membrane-damaging potential. P[5]A-isatin inclusion complexes have proved their antibiofilm potential against Staphylococcus aureus and Pseudomonas aeruginosa. The isatin was found to be released from the P[5]A-isatin inclusion complexes in a controlled manner as validated by various mathematical models. The formulated P[5]A-isatin inclusion complexes based ointment showed significant wound healing effects in vitro with 90% wound closure within 48 hours and was found to be non-toxic. Conclusively, the synthesized pillar[5]arene-isatin inclusion complexes have proved to be unique for combating wound infections and promoting the wound healing processes in an effective manner. Keywords: Biofilms, Controlled drug release, Isatin, Pillar[5]arene, Wound healing.
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Biochemistry