Session: Posters:

Lung cancer is the most common cancer type worldwide in terms of both incidence and mortality; remains to be the number one cancer killer in the US since 1980s with an estimated 135,720 deaths in 2020. In majority of the US states, incident cases remain lower for lung cancer relative to combined new cases for prostate, breast, and colon cancer, yet more people die of lung cancer every year than die of prostate, breast, and colon cancer combined. The lack of successful preventive and screening interventions in improving lung cancer survival advocates for new therapeutics to improve 5-year lung cancer survival rate (16% for men and 23% for women; 24% for non-small cell; and 6% for small cell tumors). Naturally occurring and synthetically derived naphthoquinones and their derivatives possess a wide range of biological activities such as anticancer, antimicrobial, anti-inflammatory, antiproliferative, insecticidal, hemostatic, antifertility properties. Naphthoquinone scaffold is present in some of the widely used antineoplastics such as Doxorubicin, Napabucasin, Streptonigrin, and Actinomycin; it is known to selectively target cancer cells acting as ROS-inducing agents and inhibit enzymes such as STAT3, DNA topoisomerase I and II, and AKT kinases.
Using the natural product-inspired naphthoquinone scaffold as an evolutionary selected and biologically pre-validated starting point, we have developed a distinctive set of aminonaphthoquinones, with C2 extensions that include azido, alkyne, triazole, and amino acid groups, and a representative series of amidonaphthoquinones by sequentially coupling modified Michael addition reaction with simple click or peptide chemistry. In this presentation, we will discuss the utility of our amino- and amidonaphthoquinone derivatives as lung cancer treatments while reporting new developments on a branch of synthetic organic chemistry that has been somewhat neglected despite the undeniable advantages of napthoquinone chemistry in generating biologically significant molecules. The antimicrobial properties of these amino- and amido- derivatives are under investigation.

Samir Jenkins

University of Arkansas

Appearances