Synthesis and Antibacterial Activity of Novel Derivatives of Natural Products
Abstract
Natural products have played a significant role in drug discovery, especially in infectious diseases (bacterial, fungal, parasitic, and viral) and cancer. They provide a bank of rich, complex, and highly chemically diverse structures that have evolved to acquire specific ligand-protein binding motifs over the years. The libraries of potential pharmaceutical agents generated using natural products as lead compounds have been said to generate more hits and leads than those from synthetic compounds due to the active scaffolds inherent in natural products. Antibacterial drug discovery efforts have extensively relied on natural products due to the successes recorded over time; however, antibiotic resistance to the available drugs has significantly undermined this effort as bacterial resistance keeps evolving at an alarming rate. One of the ways to ensure that chemotherapeutic agents are always available to treat these myriads of antibiotic resistance infections is to synthesize new drugs that can interact with new biological targets as well as resistance strain targets. Our research focuses on synthesizing new scaffolds through the synthetic modification of natural products with little to no biological activity. In this study, δ-lactone, a steroidal natural product with no reported biological activity, is synthetically modified by incorporating amide functionalities and macrocycle framework to generate a library of compounds that can be screened for their antibacterial activity to identify leads that will further be optimized.
Keywords:
Drug Design, Antibacterial, Novel compounds, Natural Product, Chemistry and Biochemistry
Status
Graduate
Department
Chemistry & Biochemistry
College
College of Arts and Sciences
Campus
Athens
Faculty Mentor
Bergmeier, Stephen
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Synthesis and Antibacterial Activity of Novel Derivatives of Natural Products
Natural products have played a significant role in drug discovery, especially in infectious diseases (bacterial, fungal, parasitic, and viral) and cancer. They provide a bank of rich, complex, and highly chemically diverse structures that have evolved to acquire specific ligand-protein binding motifs over the years. The libraries of potential pharmaceutical agents generated using natural products as lead compounds have been said to generate more hits and leads than those from synthetic compounds due to the active scaffolds inherent in natural products. Antibacterial drug discovery efforts have extensively relied on natural products due to the successes recorded over time; however, antibiotic resistance to the available drugs has significantly undermined this effort as bacterial resistance keeps evolving at an alarming rate. One of the ways to ensure that chemotherapeutic agents are always available to treat these myriads of antibiotic resistance infections is to synthesize new drugs that can interact with new biological targets as well as resistance strain targets. Our research focuses on synthesizing new scaffolds through the synthetic modification of natural products with little to no biological activity. In this study, δ-lactone, a steroidal natural product with no reported biological activity, is synthetically modified by incorporating amide functionalities and macrocycle framework to generate a library of compounds that can be screened for their antibacterial activity to identify leads that will further be optimized.