Pancreatic cancer, specifically Pancreatic Ductal Adenocarcinoma (PDAC) has posed a multitude of difficulties for researchers and medical doctors alike. PDAC is difficult to detect, and oftentimes goes unnoticed until standard treatments such as surgery are not feasible or simply too risky. The leading treatment for pancreatic cancer, gemcitabine, has many issues associated with delivery due to the hydrophilic nature of the two fluorines located on the 2’ Carbon of the ribose. Furthermore, when gemcitabine enters the cell, the nitrogenous portion of this cytidine nucleoside is often deaminated into uracil by cytidine deaminase which results in the exportation of the molecule out of the cell before it can reach the target protein, ribonucleotide reductase (RNR). To increase the efficacy of such molecules towards RNR, a series of novel nucleoside analogues modified at their ribose sugar have been investigated. Molecular docking studies demonstrated that these novel molecules have higher binding affinity to the target enzyme, as indicated by an increased number of H-bonding, compared to the reference drug gemcitabine. In addition, these analogues are involved in interactions with important amino acids such as S202, A605, and T607 in the active site of RNR. PASS prediction and ADMET revealed these compounds as non toxic and non carcinogenic. These results suggested that these analogues can be proposed as potential candidates for the treatment of PDAC and are worth further in vitro and in vivo investigations.

Investigation of novel nucleoside analogues as anticancer agents for the treatment of pancreatic cancer

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.