Elaboration of novel urea bearing schiff bases as potent in vitro anticancer candidates with low in vivo acute oral toxicity

Abstract

A novel series of urea Schiff base derivatives were synthesized via the condensation of o-phenylenediamine, naphthyl isocyanate and appropriate aryl aldehyde. The results of the in vitro cytotoxic activities of compounds 5a–h against cancer cells lines PC3, SKOV-3 and HeLa, revealed that almost all compounds exhibited good to moderate activities Compound 5g owing bromine atom at p-position displayed higher activity compared to homolog 5b possessing chlorine atom due to adequate diameter of bromine which is more favourable than chlorine for the inhibition activity. In addition, compound 5h is the best candidate of this series exhibiting excellent activity for three cancer cells lines. Compound 5h demonstrated also an excellent activity with IC₅₀ value of 0.6±0.3μg/mL for prostate cancer cell line PC3 and it is considered more effective than the standard drug doxorubicin Dox (IC₅₀ = 2.6±0.03μg/mL). The most active compound 5h displayed the best activity against ovarian cancer cell line SKOV3 with IC₅₀ = 1.8±0.2μg/mL. This results are higher than clinically used drug Dox (IC₅₀. 2.2±0.02μg/mL). The results of screening activities cytotoxic effect toward cervix cancer cell line HeLa, affirm that compound 5h manifest an activity with IC₅₀ value of 2.2±0.4μg/mL comparable to Dox (IC₅₀. 1.9±0.04μg/mL). In the current study, in vivo acute oral toxicity assessment of urea Schiff base hybrid compounds 5a – h indicated that there was no mortality on treated female mice during 14 days assessment test compared with the vehicle-treated group confirming the safety with LD₅₀ greater than 2000 mg/kg. In the actual study, the results affirmed that compounds 5a–h manifested in vivo no toxicity to saint cells, the compounds 5b, 5g and 5h presented higher anticancer activities against three cancer cells which authorizes promoters to use them as candidate anticancer agents.