Structural investigation of interactions between newly synthesized halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents

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Abstract This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1-D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and Raman spectroscopy, the research seeks to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties make these halogenated flavonoids potential candidates for exploring their potential for medical use.
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Structural investigation of interactions between newly synthesized halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Structural investigation of interactions between newly synthesized halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents Anita Dudek, Natalia Szulc, Aleksandra Pawlak, Paulina Strugała-Danak, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3969844/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 May, 2024 Read the published version in Scientific Reports → Version 1 posted 8 You are reading this latest preprint version Abstract This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1-D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and Raman spectroscopy, the research seeks to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties make these halogenated flavonoids potential candidates for exploring their potential for medical use. Biological sciences/Biochemistry Biological sciences/Biophysics Biological sciences/Molecular biology halogenation flavonoids derivatives liposomes ATR-FTIR cell viability fluorescent probes Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.pdf Cite Share Download PDF Status: Published Journal Publication published 08 May, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 21 Mar, 2024 Reviews received at journal 19 Mar, 2024 Reviewers agreed at journal 07 Mar, 2024 Reviewers invited by journal 04 Mar, 2024 Editor assigned by journal 04 Mar, 2024 Editor invited by journal 04 Mar, 2024 Submission checks completed at journal 04 Mar, 2024 First submitted to journal 19 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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