Design, Synthesis, Antimicrobial, and Anticancer Activities of Acridine Thiosemicarbazides Derivatives

Abstract

Background: Acridine and thiourea derivatives are important compounds in medicinal chemistry due to their diverse biological properties including anticancer and antimicrobial effects. However, literature reveals some side effects associated with use of acridines. It is suggested that hybrid molecules may reduce the side effects and enhance the beneficial properties due to synergistic activity. The objectives of the present study are to synthesize and evaluate the anticancer and antimicrobial properties of new hybrids of acridine thiosemicarbazides derivatives. Results: The structures of the synthesized compounds 4a–4e were elucidated by MS and NMR spectra. In antimicrobial assay, Compound 4c exhibited potent antimicrobial activity compared to the other four compounds. In anticancer studies, we observed that compounds 4a, 4b, 4d and 4e exhibited high cytotoxicity against the MT-4 cell line, with IC50 values of 18.42 ± 1.18, 15.73 ± 0.90, 10.96 ± 0.62 and 11.63 ± 0.11 μM, respectively. The evaluation of anticancer effects, and the associated mechanism reveals that, the anticancer activities may be related to Topo I inhibitory activity, apoptosis and cell-cycle. Molecular docking studies revealed that the presence of planar naphtho-fused rings and a flexible thiourea group together, could improve DNA-intercalation and inhibition of DNA-Topo I activity. Conclusions: The results of this study demonstrate that the rational design of target derivatives as novel antimicrobial or antitumor leads is feasible.

A new look at 9‐substituted acridines with various biological activities

“…These data suggest that the antitumor activity of derivative 1c (N-((pyridin-2-yl)methyl)acridin-9-amine) could be attributed to its DNA binding and topo I inhibition, indicating that the compound has potential for the development of novel topo I inhibitors. Chen et al (2019) carried out a topo I inhibitory activity assay on a series of acridinyl thiourea derivatives, compounds 2a-e (Figure 4), using the supercoiled DNA unwinding method. Compounds 2b, 2d, and 2e showed topo I inhibitory activity at a concentration of 0.2 μM,…”

“…The sulfurcontaining 9-anilinoacridines, derivatives 9a and 9b, were similar to m-AMSA. Compound 9b was found to have inhibited topoisomerase F I G U R E 4 Acridinyl aryl-thiourea derivatives 2a-e (Chen et al, 2019) F I G U R E 5 Structure of acridin-9-ylalkenoic derivatives 3 and 4 (Salem et al, 2015) F I G U R E 6 Structure of acridine derivatives 5-7 (Salem et al, 2015)…”

‘Acridines’ as New Horizons in Antifungal Treatment

“…The prepared analogues were active and showed inhibition against all evaluated microorganisms [14]. Acridine thiosemicarbazide derivatives ( Figure 2C) exhibited both antibacterial and antifungal activity (minimal inhibitory concentration (MIC) range 10-80 µM) as well as anticancer activity (IC50 range 10-70 µM) [15]. Although the results obtained confirmed the antifungal activity of all of the above-mentioned analogues, the probable mode of action is associated with DNA intercalation ability with the consequences for microbial cell development without being specific for fungal cells.…”

2,4-Dichlorophenoxyacetic Thiosemicarbazides as a New Class of Compounds against Stomach Cancer Potentially Intercalating with DNA

“…Our research focuses for a long time on searching for novel compounds with anticancer activity [10][11][12][13]. In particular, we focus on thiosemicarbazides as a privileged scaffold in medicinal chemistry, displaying a wide range of activities, i.e., antibacterial, antifungal, antioxidant [14][15][16][17][18], and anticancer activity [17][18][19]. Among a series of different thiosemicarbazides derivatives studied against human gastric cancer cell line MKN74, we selected two most promising based on IC 50 values.…”