Effects of new quinoline arylamidine hybrids on the leukemia and lymphoma cells' growth in vitro

Uvod: Kinolin je heterociklični organski spoj koji se sastoji od fuzioniranog benzenskog i pirimidinskog prstena koji imaju veliku sposobnost modifikacije. Upravo zbog te sposobnosti moguće je lako u laboratoriju sintetizirati različite vrste kinolinskih derivata koji su tijekom istraživanja pokazali korisna antitumorska svojstva. Derivati kinolina vrlo su atraktivni spojevi za istraživanja jer su pokazali širok spektar različitih bioloških aktivnosti, kako antitumorsku, tako i antibakterijsku, antikonvulzijsku, analgezijsku i protuupalnu. Cilj: Ispitati citotoksičnost osam različitih kinolinsko arilamidnih hibrida na četirima humanim staničnim linijama leukemija i limfoma (K562, CCRF – CEM, Raji i HuT 78). Materijali i metode: Kinolinsko arilamidni derivati sintetizirani su na Zavodu za primijenjenu kemiju i ekologiju pri Prehrambeno – tehnološkom fakultetu u Osijeku, a stanične linije su komercijalno kupljene. Derivati su otopljeni u DMSO-u kao koncentrirane 1·10-2 M otopine, dok su razrjeđenja pripremljena neposredno prije aplikacije na stanice te nanesena u koncentracijama od 1·10⁻⁴ M, 1·10⁻⁵ M i 1·10⁻⁶ M. Citotoksičnost primijenjenih spojeva utvrđena je korištenjem MTT testa te očitanjem apsorbancija na spektrofotometru. Rezultati: Uočeno je kako koncentracije derivata od 1·10⁻⁵ M te pogotovo od 1·10⁻⁶ M kod svih staničnih linija ne uzrokuju značajan inhibicijski učinak. Značajan inhibicijski učinak pokazali su svi derivati aplicirani u koncentraciji od 1·10⁻⁴ M, ali je učinak bio najbolji pri primjeni derivata 2 i 8. Najveću osjetljivost na primijenjene derivate pokazala je stanična linija HuT 78. Zaključak: Kinolinsko arilamidni hibridi smanjuju rast tumorskih stanica leukemija i limfoma, ali postotak inhibicije ovisi o koncentraciji spoja i vrsti stanične linije.Introduction: Quinoline is a heterocyclic organic compound consisting of a fused benzene and pyrimidine ring which have a high modification ability. Precisely because of this ability it is possible to synthesize various types of quinoline derivatives which have shown useful anti-tumor properties during the study. Quinoline derivatives are very attractive compounds for research as they have shown a wide spectrum of various biological activities, both antitumor and antibacterial, anticonvulsant, analgesic and anti-inflammatory. Objective: To investigate the cytotoxicity of eight different quinoline arylamidine hybrids in four human cell lines of leukemia and lymphoma (K562, CCRF - CEM, Raji and HuT - 78). Materials and Methods: Quinoline arylamidine derivatives were synthesized at the Institute of Applied Chemistry and Ecology at the Faculty of Food Technology in Osijek, and the cell lines were commercially purchased. The derivatives were dissolved in DMSO as a concentrated 1·10⁻2 M solution prior to use in the study, while the dilutions were prepared immediately prior to application to the cells and applied at concentrations of 1·10 ⁻⁴ M, 1·10⁻⁵ M and 1·10⁻⁶ M. Cell culture was carried out in an incubator at 5% of carbon (IV) dioxide, at a temperature of 37°C and with high humidity. The cytotoxicity of the applied compounds was determined using the MTT test and by reading the absorbance on the spectrophotometer. Results: Concentrations of 1·10⁻⁵ M and of 1·10⁻⁶ M in all cell lines are observed to cause no significant inhibitory effect. Significant inhibitory effect on the investigated cell lines showed all derivatives applied at a concentration of 1·10⁻⁴ M but the effect was the best when using derivatives 2 and 8. Generally, the highest susceptibility to the derivatized derivatives was demonstrated by the HuT-78 cell line. Conclusion: Quinoline arylamidine hybrids reduce the growth of tumor cells of leukemia and lymphoma, but the percentage of inhibition depends on the concentration of the compound and the cell line type