The synthesis and biological evaluation of alkyl and benzyl naphthyridinium analogs of eupolauridine as potential antimicrobial and cytotoxic agents

Shahriyar Taghavi-Moghadam; Cecil D Kwong; John A Secrist 3rd; Shabana I Khan; Alice M Clark

doi:10.1016/j.bmc.2016.02.028

The synthesis and biological evaluation of alkyl and benzyl naphthyridinium analogs of eupolauridine as potential antimicrobial and cytotoxic agents

Bioorg Med Chem. 2016 Dec 1;24(23):6119-6130. doi: 10.1016/j.bmc.2016.02.028. Epub 2016 Feb 23.

Authors

Shahriyar Taghavi-Moghadam¹, Cecil D Kwong¹, John A Secrist 3rd², Shabana I Khan³, Alice M Clark³

Affiliations

¹ Organic Chemistry Department, Southern Research Institute, 2000 Ninth Avenue South, PO Box 55305, Birmingham, AL 35255, United States.
² Organic Chemistry Department, Southern Research Institute, 2000 Ninth Avenue South, PO Box 55305, Birmingham, AL 35255, United States. Electronic address: secrist@southernresearch.org.
³ National Center for Natural Products Research, and Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, United States.

PMID: 27769668
DOI: 10.1016/j.bmc.2016.02.028

Abstract

Eupolauridine, an indenonaphthyridine alkaloid, has been previously reported by us to exhibit antifungal activity. This study describes the synthesis of new alkyl and benzyl naphthyridinium/pyridinium analogs of eupolauridine as potential antifungal agents. A majority of the analogs exhibited antifungal activity against opportunistic pathogens such as Candida albicans and Cryptococcus neoformans. Several of them were also effective against bacteria (Staphylococcus aureus, MRS, Pseudomonas and Mycobacterium) and the malaria parasite (Plasmodium falciparum) to variable extents. A number of analogs were also cytotoxic to human cancer cell lines.

Keywords: Antibacterial; Antifungal; Antimicrobial; Eupolauridine analogs.

MeSH terms

Amphotericin B / pharmacology
Animals
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / pharmacology
Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / pharmacology
Antimalarials / chemical synthesis
Antimalarials / pharmacology
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Aspergillus fumigatus / drug effects
Candida albicans / drug effects
Cell Line, Tumor
Chlorocebus aethiops
Cryptococcus neoformans / drug effects
DNA Topoisomerases, Type I / metabolism
Humans
Indenes / chemical synthesis
Indenes / pharmacology
Naphthyridines / chemical synthesis
Naphthyridines / pharmacology*
Plasmodium falciparum / drug effects
Structure-Activity Relationship
Topoisomerase I Inhibitors / chemical synthesis
Topoisomerase I Inhibitors / pharmacology
Vero Cells

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Antimalarials
Antineoplastic Agents
Indenes
Naphthyridines
Topoisomerase I Inhibitors
eupolauridine
Amphotericin B
DNA Topoisomerases, Type I
TOP1 protein, human