OMA1520 and OMA1774, novel 1,2,4-triazole bearing analogs of combretastatin A-4, inhibit hepatocellular carcinoma: Histological and immunohistochemical studies

Abstract

Combretastatin A-4 (CA-4) received significant interest as a potential anticancer agent in recent years. Several CA-4 analogs were synthesized and investigated to enhance the activity or solve the in vivo decreased activity of CA-4. AimThe present study aims to investigate the chemotherapeutic and the antiproliferative effects of the mono and the dual therapy of the newly synthesized CA-4 analogs OMA1520 and OMA1774 against hepatocellularcarcinoma (HCC) induced in male adult rats by N-methylnitrosourea (MNU). Methods50 male rats were divided into 5 groups of 10 animals in each group. Group I: normal healthy control; group II: MNU treated group, group III: MNU animals treated by OMA1520, group IV: MNU animals treated by OMA1774, and group V: MNU animals treated by both OMA1520 and OMA1774. The rats were assessed for liver cancer progression or inhibition by evaluating the histopathological, immunohistochemical, biochemical, and antioxidant enzyme status. ResultsThe present work indicated that OMA1520 and OMA1774 possessed substantial chemotherapeutic efficiency against HCC. The histological and immunohistochemical examinations of liver tissues confirmed the biochemical sera data. Also, they diminished the cytotoxic effects of MNU and restored the normal histological hepatic architecture. Both analogs restored the normal levels of liver enzymes and functions and revealed potential antioxidant effects. OMA1520 and OMA1774 reduced the inflammatory and tumor markers' elevated expressions in serum. ConclusionSubstantial evidence in our results suggests that both CA-4 analogs could be possible alternative anticancer agents, and their co-administration provides a synergistic activity.