Design, synthesis and evaluation of antitumor activity of new rotundic acid acylhydrazone derivatives

Abstract

In light of the important antitumor activity of acylhydrazone compounds and based on our previous study, 18 new rotundic acid (RA) acylhydrazone derivatives were synthesized. All of the compounds were characterized by their spectroscopic data. The antiproliferative activity of the compounds was evaluated in vitro via the MTT method in three tumor cell lines, including A-375 (human malignant melanoma cells), SPC-A1 (human lung adenocarcinoma) and NCI-H446 (small cell lung cancer). The results showed that the antiproliferative activity of all of the compounds on the NCI-H446 cell line did not increase compared to RA, however, most of the derivatives exhibited higher activity against the A375 and SPC-A1 cell lines as compared to RA. Importantly, the antiproliferative activities of compounds 5a and 5b were the highest among the compounds, with IC(50) values <10 μM. Collectively, compounds 5a and 5b may act as potential anti-tumor agents in the future.

Synthesis of some new acylhydrazone compounds containing the 1,2,4-triazole structure and their neuritogenic activities in Neuro-2a cells

“…1A). For this experiment, cells were seeded in wells of 96-well plate and maintained in culture medium for 24 h. The cells were then treated with test compounds (5,10,20, 50 mM concentration of each compound) for 24 h. As indicated in Fig. 1B, the compounds A0, A1, A2, A3, A4, A5, A7 and A8 showed that the dependence of cell viability on concentration is clearly noticed.…”

“…9,10 In recent years, researchers have found that acylhydrazone compounds exhibit many benecial biological activities, such as anti-bacterial, [11][12][13] anti-inammatory, [14][15][16] anti-viral 17,18 and anti-tumor activities. [19][20][21] However, there are currently few studies on the neuroactivity of acylhydrazone compounds.…”

Absolute bioavailability, dose proportionality, and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method

“…Rotundic acid (RA), a plant-derived and ursane-type pentacyclic triterpene acid, was identified as a major active ingredient of IRC and has been shown to exert extensive pharmacological effects, including antimicrobial [ 3 , 4 ], anti-inflammatory [ 5 ], anticancer [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] ], and lipid-decreasing effects [ 14 ]. It has also been proven to alleviate type 2 diabetes and its complications by improving the composition of the gut microbiota [ 15 ].…”

Rotundic acid induces Cas3‑MCF‑7 cell apoptosis through the p53 pathway

“…Accumulative data concerning TCM have shown marked activity with regard to the effects on the tumor cell death pathway, which can guide tumor treatment decisions and clinical management (9). Currently, compounds with unique chemical entities that are derivatives of natural medicines are a considerable resource for the development of novel medicines (10). Rotundic acid (RA; Fig.…”