Antimicrobial, cytotoxic and genotoxic activity of newly synthetised palladium(II) and platinum(II) complexes with 2-(diphenylphosphino) benzaldehyde 1-adamantoylhydrazone

Klinička primena hemioterapeutskih agenasa u lečenju infektivnih bolesti i kancera sa sobom nosi brojna ograničenja, usled mogućeg neselektivnog, genotoksičnog i mutagenog dejstva, pojave rezistencije i ozbiljnih neželjenih efekata, što ukazuje na permanentnu potrebu za otkrivanjem i ispitivanjem biološki aktivnih agenasa koji bi mogli biti značajni za razvoj novih hemioterapeutskih lekova. Istraživanja sprovedena u poslednjoj deceniji otkrila su vrlo perspektivne antimikrobne i antikancerske potencijale derivata 2-(difenilfosfino)benzaldehida i njihovih kompleksa sa prelaznim metalima. U ovom radu je ispitivana in vitro antimikrobna, citotoksična i genotoksična aktivnost novosintetisanih kompleksa Pd(II) i Pt(II) sa 2-(difenilfosfino)benzaldehid-1- adamantoilhidrazonom kao ligandom. U okviru antimikrobne aktivnosti ispitana je i antimikobakterijska i antivirusna aktivnost, koje do sada nisu ispitivane na srodnim jedinjenjima. Ligand i njegovi kompleksi Pd(II) i Pt(II) ispoljili su umereno ili slabo antimikrobno dejstvo na pojedine referentne sojeve bakterija u poređenju sa poznatim antimikrobnim lekovima, a ligand je pokazao snažno bakteriostatičko i baktericidno dejstvo na atenuisanom soju M. bovis Bacillus Calmette-Guérin. Ispitivana jedinjenja imaju dozno-zavisan citotoksični efekat prema normalnoj i malignim ćelijskim linijama, u opsegu aktivnosti referentnih citostatika karboplatine i oksaliplatine. Najbolja citotoksična aktivnost detektovana je na Hep-2 ćelijama poreklom iz kancera larinksa, a najslabiju aktivnost ligand i njegovi Pd(II) i Pt(II) kompleksi pokazali su na A549 ćelijama poreklom iz adenokarcinoma pluća. Zdrave ćelije pluća MRC-5 pokazale su visok stepen otpornosti na ispitivana jedinjenja. Detektovana je visoko-selektivna aktivnost svih ispitivanih supstanci prema kancerskim ćelijama Hep-2. Ostvarena je citotoksična aktivnost liganda prema A549 ćelijama, značajno bolja od karboplatine. Rezultati citotoksične aktivnosti usmerili su dalja istraživanja i na druge aspekte antikancerskog dejstva, pa je ispitan uticaj na proliferaciju ćelija i citostatsko dejstvo, ispitana je indukcija programirane ćelijske smrti, a kao važan element antimetastatske aktivnosti ispitan je i uticaj na migratorni potencijal ciljnih ćelija...The clinical use of chemotherapeutic agents in the treatment of infectious diseases and cancers is limited due to nonselective, genotoxic and mutagenic effects, resistance development and serious side effects. There is a constant need for new biologically active agents which could be used to develop new chemotherapeutic drugs. Research conducted in the last decade have revealed very promising antimicrobial and anticancer potential of 2-(diphenylphosphino)benzaldehyde derivatives and its complexes with transition metals. In this study, antimicrobial, cytotoxic and genotoxic activity of newly synthetised Pd(II) and Pt(II) complexes, with 2-(diphenylphosphino)benzaldehyde 1- adamantoylhydrazone as a ligand, were investigated in vitro. The antimicrobial activity testing included antimycobacterial and antiviral activity tests, which have not yet been studied in related compounds. In comparison with well known antimicrobial agents, ligand and its Pd(II) and Pt(II) complexes exhibited a low to medium antimicrobial effect on the tested bacterial strains. The ligand had strong bacteriostatic and bactericidal effect on the attenuated M. bovis Bacillus Calmette-Guérin strain. Tested compounds exibited dose-dependent cytotoxic effects on normal and cancer cell lines, within the activity range of cytostatics carboplatin and oxaliplatin. The highest cytotoxicity of the compounds was detected in larynx cancer Hep-2 cells and the lowest in A549 lung adenocarcinoma cells. The MRC-5 cells, derrived from normal lung tissue, manifested high tolerance to the tested compounds. The compounds were characterized by relatively high cytotoxicity in cancerous Hep-2 cells when compared to healthy MRC-5 cells. The results obtained from the examination of cytotoxicity in A549 cells revealed that the ligand displays cytotoxic activity which is markedly higher than that of carboplatin. The results which showed the cytotoxic potential of the tested compound directed further research towards their other anticancer attributes, such as their influence on cell proliferation and cytostatic activity, induction of programmed cell death, and impact on cell motility potential which is an important aspect of antimetastatic activity..