Discovery of spirooxindole-pyrrolidine heterocyclic hybrids with potent antifungal activity against fungal pathogens

Author:

Dowdy Hannah1,Kumar Raju Suresh2,Almansour Abdulrahman I2,Arumugam Natarajan2,Ibrahim Alaqeel Shatha3,Thangamani Shankar145ORCID

Affiliation:

1. College of Veterinary Medicine, Midwestern University , 19555 N. 59th Ave. , Glendale, AZ 85308, United States

2. Department of Chemistry, College of Science, King Saud University , PO Box 2455, Riyadh 11451, Saudi Arabia

3. Department of Chemistry, College of Science, King Saud University , (034), Riyadh 11495, Saudi Arabia

4. Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University , West Lafayette, IN 47906, United States

5. Purdue Institute for Immunology, Inflammation and Infectious Diseases (PI4D) , IN 47906, United States

Abstract

Abstract Fungal pathogens mainly Candida and Cryptococcus species causes serious life-threating infections to humans, especially in individuals who are immunocompromised. Increasing frequency of antifungal drug resistance along with paucity of FDA-approved drugs suggest a dire need for new antifungal drugs. Our screening of newly synthesized spirooxindole heterocyclic hybrid compounds revealed that the novel small molecule, DPA-3, has potent antifungal activity without inducing mammalian cell cytotoxicity. Furthermore, DPA-3 significantly reduced hyphal and biofilm formation of Candida albicans ATCC 10231 strain, out-competing two FDA approved antifungal drugs. The results of our study conclude that DPA-3 is a compelling candidate for further development as an antifungal drug.

Funder

King Saud University

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,General Medicine,Immunology and Allergy

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