The unifying theme of Kornienko’s research projects is the discovery of novel synthetic organic chemistry and its utilization for anticancer drug discovery. For example, in the ongoing projects we discovered new multicomponent reactions allowing for the constructions of fused pyrazolodihydropyridine and pyrrolopyrimidine rings leading to novel heterocycles shown in the scheme below. Biological evaluation of these molecules revealed their low nanomolar antiproliferative activities against various cancers, especially melanoma and glioblastoma, characterized with dismal clinical prognoses. It is important that these highly potent molecules can be made through 4-component reactions in one step from commercially available reagents.

Our cancer drug discovery work emphasizes the development of innovative methods to combat apoptosis-resistant cancers, such as melanoma, glioblastoma, lung cancer, among others. Thus, much effort is applied toward the identification and investigation of natural products that exhibit antimetastatic properties at non-toxic concentrations or induce non-apoptotic cancer cell death, such as programmed necrosis, autophagy, or paraptosis. We collaborate with a large group of cancer biologists and clinicians in the US and Europe. Examples of natural products, which are currently studied in Dr. Kornienko’s lab, are shown below.