Synthesis and Application in Cell Imaging of Acridone Derivatives

Abstract

Tricyclic acridone derivatives have been extensively developed as antimicrobial, antimalarial, and antitumor drugs due to their broad spectrum of drug design and biological activity. In this study, we developed a surfactant-like acridone scaffold that contained two vinylpyridines and a dodecyl pyridine chain. The acridone scaffold decorated the dodecyl pyridine chain by N-bromosuccinimide reagent. The surfactant-like core scaffold incorporated with 4-vinylpyridines at the 2- and 7-positions via a Heck coupling reaction. Subsequently, the acridone derivatives were methylated onto these pyridine groups. Here we developed two similar acridone derivatives, MedAcd12C and MedAcd12P. The MedAcd12C incorporated two pyridine groups, and MedAcd12P incorporated three pyridine groups. MedAcd12C and MedAcd12P have two identical vinylpyridines and the different anchor tails at the N10 position. Their physicochemical properties, cell compatibility, and photoluminescence were demonstrated. Although both compounds have no fluorescence emission in water solution, MedAcd12P and MedAcd12C significantly appeared with orange light emission in the cellular imaging. We suggested that the surfactant-like scaffold promoted the drugs’ self-assembly and caused the aggregation-induced emission (AIE) after cellular uptake. This innovative design endowed acridone derivatives with an AIE and traceability for cell imaging.

Newly synthesized acridone derivatives targeting lung cancer: A toxicity and xenograft model study

“…They possess various bioactivities such as anticancer (Xu et al, 2019), antitubercular (Tripathi et al, 2006), anti‐inflammatory (Chen et al, 2002), antimalarial (Dodean et al, 2019), antiparasitic (Carole et al, 2005), antipsoriatic (Putic et al, 2010), antimicrobial (Kaya et al, 2011), antiviral (Mazzucco et al, 2015), anticandidiasis, and antibiofilm (Oliveira et al, 2019). Acridones can function as deoxyribonucleic acid (DNA) intercalators via blocking topoisomerase and telomerase enzymes due to their distinctive planar ring structure (Chan et al, 2020). A few of their derivatives include N‐(2‐(dimethylamino) ethyl) acridine‐4‐carboxamide (1) , triazoloacridone (2) , and amsacrine (3) are under clinical trials (Rupar et al, 2020).…”

“…Acridones can function as deoxyribonucleic acid (DNA) intercalators via blocking topoisomerase and telomerase enzymes due to their distinctive planar ring structure (Chan et al, 2020). A few of their derivatives include N-(2-(dimethylamino) ethyl) acridine-4carboxamide (1), triazoloacridone (2), and amsacrine (3) are under clinical trials (Rupar et al, 2020).…”

“…In vivo nude mice xenografted tumor model established by MCF-7 cells showed that acridone could induce cell apoptosis via inhibition of the ABCG2 (ATP-binding cassette subfamily G member 2) protein used for the treatment of breast cancer (Xia et al, 2018). Multi-substituted benzyl acridone derivative (7) unveiled that compound (7) effectively suppressed the growth of HepG2 xenograft tumors in vivo by 54% after 30 days of treatment (Chan et al, 2020). Hence, acridone scaffolds have drawn the attention of medicinal chemists to synthesize novel derivatives (Figure 1).…”

Impact of engineering on medicine: a literature review

“…The new medical challenges include the application of traditional medical knowledge and its linkage with new technological trends. The contribution of engineering in medical processes [1], [2] has meant greater efficiency in clinical diagnosis and turn the discovery of new ways to address the most complex health problems.…”