Molecular and Functional Interactions Between Cisplatin and Nicotinamide: A Combined Computational, Spectroscopic,...

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Cisplatin is a vital chemotherapy drug, but its efficacy is limited by toxicity and drug interactions.
• Nicotinamide (vitamin B3), a NAD+ precursor, influences cellular metabolism and DNA repair, potentially affecting chemotherapy responses.

Purpose of the Study:

• To investigate the molecular and biological interactions between Cisplatin and Nicotinamide.
• To explore how Nicotinamide might modulate cellular responses to Cisplatin chemotherapy.

Main Methods:

• Chemical synthesis of a novel Cisplatin-Nicotinamide complex.
• Density Functional Theory (DFT) for computational analysis of interactions.
• In vitro biological assays using non-small cell lung cancer cell lines (A549, PC-9).

Main Results:

• A novel cis-[Pt(NH3)2NicotinamideCl]NO3 complex was synthesized and structurally analyzed.
• DFT calculations showed favorable Nicotinamide coordination to Cisplatin hydrolysis products.
• Nicotinamide pre-treatment reduced Cisplatin cytotoxicity in vitro; the pre-formed complex showed no anticancer effects.

Conclusions:

• Nicotinamide may interact with reactive Cisplatin species, reducing the availability of active platinum(II) species.
• This study provides mechanistic insights into potential drug-nutrient interactions in platinum-based chemotherapy.
• Further research under clinical conditions is needed to validate these findings.