Synthesis of 1,10-Phenanthroline Compounds Containing Azolium Salts and Studies on Their Anticancer Activity

Project no. 32327 · Status: Kapanmış · 2024

Summary

<p>Cancer&nbsp;is&nbsp;the&nbsp;most&nbsp;common&nbsp;disease,&nbsp;claiming&nbsp;hundreds&nbsp;of&nbsp;thousands&nbsp;of&nbsp;lives&nbsp;worldwide.&nbsp;According&nbsp;to&nbsp;the&nbsp;WHO,&nbsp;cancer&nbsp;cases&nbsp;are&nbsp;expected&nbsp;to&nbsp;rise&nbsp;to&nbsp;22&nbsp;million&nbsp;in&nbsp;the&nbsp;next&nbsp;twenty&nbsp;years.&nbsp;Due&nbsp;to&nbsp;the&nbsp;rapid&nbsp;increase&nbsp;in&nbsp;cancer&nbsp;cases&nbsp;globally,&nbsp;a&nbsp;proper&nbsp;understanding&nbsp;of&nbsp;the&nbsp;disease&nbsp;and&nbsp;the&nbsp;development&nbsp;of&nbsp;new,&nbsp;effective,&nbsp;non-toxic,&nbsp;and&nbsp;cheaper&nbsp;drugs&nbsp;for&nbsp;treatment&nbsp;are&nbsp;crucial.&nbsp;Currently,&nbsp;platinum&nbsp;and&nbsp;its&nbsp;derivatives&nbsp;are&nbsp;used&nbsp;in&nbsp;cancer&nbsp;treatment.&nbsp;However,&nbsp;these&nbsp;platinum&nbsp;complexes&nbsp;become&nbsp;ineffective&nbsp;as&nbsp;cells&nbsp;develop&nbsp;resistance&nbsp;to&nbsp;these&nbsp;drugs&nbsp;over&nbsp;time;&nbsp;they&nbsp;also&nbsp;exhibit&nbsp;serious&nbsp;side&nbsp;effects&nbsp;such&nbsp;as&nbsp;nephrotoxicity,&nbsp;neurotoxicity,&nbsp;ototoxicity,&nbsp;nerve&nbsp;damage,&nbsp;hair&nbsp;loss,&nbsp;nausea,&nbsp;vomiting,&nbsp;and&nbsp;abdominal&nbsp;pain.&nbsp;Ruthenium&nbsp;complexes&nbsp;are&nbsp;a&nbsp;new&nbsp;generation&nbsp;of&nbsp;metal&nbsp;anti-tumor&nbsp;drugs&nbsp;currently&nbsp;attracting&nbsp;significant&nbsp;attention&nbsp;in&nbsp;multidisciplinary&nbsp;research.&nbsp;Studies&nbsp;suggest&nbsp;that&nbsp;ruthenium&nbsp;complexes&nbsp;penetrate&nbsp;tumor&nbsp;cells&nbsp;well&nbsp;and&nbsp;bind&nbsp;effectively&nbsp;to&nbsp;DNA.&nbsp;Ruthenium&nbsp;complexes&nbsp;are&nbsp;currently&nbsp;of&nbsp;great&nbsp;interest&nbsp;as&nbsp;anticancer&nbsp;agents&nbsp;in&nbsp;the&nbsp;fields&nbsp;of&nbsp;biology,&nbsp;pharmaceuticals,&nbsp;and&nbsp;medicinal&nbsp;chemistry.&nbsp;The&nbsp;intercalation&nbsp;properties&nbsp;of&nbsp;the&nbsp;phenanthroline&nbsp;ligand&nbsp;into&nbsp;the&nbsp;DNA&nbsp;helix,&nbsp;the&nbsp;electronic&nbsp;and&nbsp;biological&nbsp;properties&nbsp;of&nbsp;imidazole&nbsp;derivatives,&nbsp;and&nbsp;the&nbsp;cytotoxic&nbsp;properties&nbsp;of&nbsp;ruthenium&nbsp;metal&nbsp;inevitably&nbsp;lead&nbsp;to&nbsp;the&nbsp;emergence&nbsp;of&nbsp;highly&nbsp;active&nbsp;species.&nbsp;This&nbsp;project&nbsp;aims&nbsp;to&nbsp;synthesize&nbsp;new&nbsp;and&nbsp;effective&nbsp;Ru(II)&nbsp;paracimene&nbsp;monometallic&nbsp;complexes&nbsp;containing&nbsp;phenanthroline&nbsp;and&nbsp;imidazole&nbsp;derivatives,&nbsp;which&nbsp;are&nbsp;not&nbsp;currently&nbsp;reported&nbsp;in&nbsp;the&nbsp;literature,&nbsp;and&nbsp;to&nbsp;investigate&nbsp;their&nbsp;cytotoxic&nbsp;properties&nbsp;in&nbsp;cancerous&nbsp;cell&nbsp;lines.&nbsp;The&nbsp;structures&nbsp;of&nbsp;the&nbsp;synthesized&nbsp;ruthenium&nbsp;complexes&nbsp;will&nbsp;be&nbsp;characterized&nbsp;using&nbsp;FTIR,&nbsp;1H,&nbsp;13C,&nbsp;19F,&nbsp;31P&nbsp;NMR&nbsp;spectroscopy,&nbsp;UV-visible&nbsp;spectroscopy,&nbsp;mass&nbsp;spectroscopy,&nbsp;and&nbsp;XRD&nbsp;analysis.&nbsp;The&nbsp;antitumor&nbsp;properties&nbsp;of&nbsp;the&nbsp;synthesized&nbsp;and&nbsp;characterized&nbsp;complexes&nbsp;will&nbsp;be&nbsp;evaluated&nbsp;in&nbsp;vitro&nbsp;using&nbsp;human&nbsp;breast&nbsp;cancer&nbsp;cell&nbsp;line&nbsp;(MCF-7),&nbsp;triple-negative&nbsp;breast&nbsp;cancer&nbsp;cell&nbsp;line&nbsp;(MDA-MB-231),&nbsp;and&nbsp;non-tumorigenic&nbsp;epithelial&nbsp;cell&nbsp;line&nbsp;(MCF-10A).&nbsp;The&nbsp;cytotoxic&nbsp;activity&nbsp;of&nbsp;each&nbsp;Ru-monometallic&nbsp;complex&nbsp;against&nbsp;cancer&nbsp;cells&nbsp;will&nbsp;be&nbsp;determined&nbsp;at&nbsp;four&nbsp;different&nbsp;concentrations&nbsp;using&nbsp;MTT&nbsp;(3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium&nbsp;bromide)&nbsp;analysis.&nbsp;To&nbsp;evaluate&nbsp;the&nbsp;synthesized&nbsp;ruthenium&nbsp;complexes&nbsp;as&nbsp;potent&nbsp;cytotoxic&nbsp;agents,&nbsp;their&nbsp;ability&nbsp;to&nbsp;bind&nbsp;DNA&nbsp;and&nbsp;serum&nbsp;albumin&nbsp;and&nbsp;enter&nbsp;cells,&nbsp;their&nbsp;effect&nbsp;on&nbsp;apoptosis&nbsp;and&nbsp;autophagy&nbsp;proteins&nbsp;using&nbsp;western&nbsp;blot,&nbsp;and&nbsp;the&nbsp;stage&nbsp;of&nbsp;cell&nbsp;death,&nbsp;particularly&nbsp;apoptosis,&nbsp;will&nbsp;be&nbsp;investigated&nbsp;using&nbsp;Annexin&nbsp;V-FITC/PI.&nbsp;This&nbsp;project&nbsp;will&nbsp;reveal&nbsp;the&nbsp;effective&nbsp;role&nbsp;of&nbsp;metal-based&nbsp;drugs&nbsp;in&nbsp;the&nbsp;treatment&nbsp;of&nbsp;breast&nbsp;cancer&nbsp;within&nbsp;the&nbsp;field&nbsp;of&nbsp;medical&nbsp;bioinorganic&nbsp;chemistry,&nbsp;through&nbsp;approaches&nbsp;to&nbsp;the&nbsp;design&nbsp;and&nbsp;application&nbsp;of&nbsp;innovative&nbsp;metal-based&nbsp;drugs.</p>

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