Deciphering the Influence of Cigarette Smoke Carcinogens on CNS Associated Biomolecules: A Computational Synergistic Approach.

Abstract

Human health issues caused by Cigarette Smoke Carcinogens (CSC) are increasing rapidly every day and challenging the scientific community to provide a better understanding in order to avoid its impact on communities. Cigarette smoke also contains tobacco-based chemical compounds harmful to human beings, either smokers or non-smokers. We have tested 7H-Dibenzo[c,g]carbazole (7H-DBC) and Dibenz[a,h]acridine (DBAD) derivatives of Asz-arenes along with N'-Nitrosoanabasine (NAB) and N-Nitrosoanatabine (NAT) derivatives of N-Nitrosamines molecular interaction with CNS biomolecules. Computational synergistic approaches like system biology and molecular interaction techniques were implemented to conduct the analysis. CSC efficiently interacted with NRAS, KRAS, CDH1, and RAC1 molecular targets in CNS. We have also performed the interactome analysis followed by system biology approaches and found that HSPA8 is the most important hub protein for the network generated for CSC-hampered genes of CNS. We have also identified 6 connector proteins, namely TP53, HSP90AA1, PPP2CA, CDH1, CTNNB1, and ARRB1. Further analysis revealed that NRAS and CDH1 have maximum interactions with all the selected CSC. The obtained structural analysis data could be utilized to assess the carcinogenic effect of CSC and could be useful in the treatment of CNS diseases and disorders induced, especially by tobacco-specific carcinogens, or it could also be used in vivo/ in vitro experimentation model designing.