Exploring the potential of fluoro‐flavonoid derivatives as anti‐lung cancer agents: DFT, molecular docking, and molecular dynamics techniques

Abstract

The present investigation utilized in silico methodologies to explore the diverse pharmacological activities, toxicity profiles, and chemical reactivity of a series of fluoro‐flavonoid compounds (1–14), which are secondary metabolites of plants known for their broad range of biological effects. A comprehensive strategy is utilized, incorporating methods such as prediction of activity spectra for substances (PASS) prediction, absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments, and density functional theory (B3LYP) calculations using three basis sets: 6‐31G(d,p), 6‐311G(d,p), and 6‐311++G(d,p). Furthermore, the study employed molecular docking technique to identify target proteins, including HER2 (7JXH), EGFR (4UV7), FPPS (1YQ7), HPGDS (1V40), DCK (1P60), and KEAP1 on Nrf2 (1X2J), for the investigated compounds, with cianidanol and genistein serving as reference drugs for the docking process. The investigated fluoro‐flavonoid compounds exhibited significantly greater binding affinities (ranging from −8.3 to −10.6 kcal mol−1) toward HER2, HPGDS, and KEAP1 compared to the reference drugs, cianidanol and genistein, which displayed binding affinities ranging from −8.4 to −9.4 kcal mol−1. Furthermore, molecular dynamics simulations were conducted to assess the stability of the protein‐ligand interaction, using the root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), Radius of gyration (Rg) parameters and principle component analysis (PCA). Among the tested fluoro‐flavonoid analogs, analog 11 showed a RMSD value of .15 nm with the HER2 protein target, indicating a stable interaction. Based on in silico results, it appears that the fluoro‐flavonoid compound 11 has the potential to serve as a targeted anti‐lung cancer drug. However, additional in vivo and in vitro studies are necessary to confirm this hypothesis.

Investigating Baxdrostat and Its Derivatives as Aldosterone Synthase Inhibitors for Resistant Hypertension: An In Silico Approach

“…[37] An equilibration process was conducted to ensure system stability, utilizing position-restrained dynamics (NVT) at 300 K for 3000 ps, implemented with the leapfrog algorithm. [12,13,38] Following this equilibration phase, the entire system underwent a production run for an additional 3000 ps under constant temperature and pressure conditions. Subsequently, the system was further simulated for 20 ns at the same temperature and pressure.…”

“…[10] Studies by Uddin et al [12,13] have shown that certain chemical derivatives have the potential to fight cancer. The first study [12] investigated benzylidinemalononitrile and ethyl 2-cyano-3-phenylacrylate derivatives, while the second [13] focused on fluoro-flavonoid derivatives. Both studies provide valuable insights into the anti-cancer properties of these compounds.…”

“…No drug‐related severe side effects or adrenocortical insufficiency cases were reported [10] . Studies by Uddin et al [12,13] . have shown that certain chemical derivatives have the potential to fight cancer.…”

“…Both studies provide valuable insights into the anti‐cancer properties of these compounds. The in silico approach employed in the second study [13] offers a computational perspective that can inform further experimental research and potential medical and biological applications.…”

“…No drug-related severe side effects or adrenocortical insufficiency cases were reported. [10] Studies by Uddin et al [12,13] have shown that certain chemical derivatives have the potential to fight cancer. The first study [12] investigated benzylidinemalononitrile and ethyl 2-cyano-3-phenylacrylate derivatives, while the second [13] focused on fluoro-flavonoid derivatives.…”