TITLE:
Cyclic Nucleotide Structural Differentiation of Compounds Modulating Apoptosis and Drug Resistance
AUTHORS:
Wynford Robert Williams
KEYWORDS:
Cancer, Chemotherapy, Guanosine Cyclic Monophosphate, Molecular Similarity, Multidrug Resistance
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.9 No.8,
August
4,
2021
ABSTRACT: Carcinogenesis is associated with malfunction in the cGMP-mediated regulation of cytosolic Ca2+ and reactive oxygen species. Chemotherapy resistant cancer cells are re-sensitised to apoptosis by the action of a substantial number of natural compounds on cell membrane multidrug resistant proteins. Chemical structures of pro-apoptotic and anti-apoptotic compounds demonstrate relative molecular similarity to cGMP. This study uses a computational chemistry program to investigate molecular similarity within cGMP and chemo-preventative structures. Chemotherapeutic drugs and resistance modulators provide multiple fits to a nucleotide template that differ in their relationship to the cyclised ring of cGMP. The alternative fits of drug and modulator structures may relate to the development and unblocking of apoptosis and drug resistance.