<p>Synthesis and antitumor activity of novel pyridinium fullerene derivatives</p>

Abstract

Purpose We have previously reported that some cationic fullerene derivatives exhibited anticancer activity, and they are expected to be a potential lead compound for an anti-drug resistant cancer agent. However, they are bis-adducts and a mixture of multiple regioisomers, which cannot be readily separated due to the variability of substituent positions on the fullerene cage. To overcome this issue, we evaluated the antiproliferative activities of a set of mono-adduct derivatives and examined their structure-activity relationship. In addition, the in vivo antitumor activity of selected derivatives was also examined. Methods Nineteen pyridinium fullerene derivatives were newly designed and synthesized in this study. Their antiproliferative activities were evaluated using several cancer cell lines including drug-resistant cells. Furthermore, in vivo antitumor activity of several derivatives was investigated in mouse xenograft model of human lung cancer. Results The derivatives inhibited the proliferation of cancer cell lines, including cisplatin-resistant cells and doxorubicin-resistant cells. It was also shown that compound 10 (10 μM), 13 (10 μM) and cis - 14 (10 μM) induced the intracellular oxidative stress. In addition, compound 13 (20 mg/kg) and cis - 14 (15 mg/kg) significantly exhibited antitumor activity in mouse xenograft model of human lung cancer. Conclusion We synthesized a novel set of mono-adduct fullerene derivatives functionalized with pyridinium groups and found that most of them show potent antiproliferative activities against cancer cell lines and some of them show significant antitumor activities in vivo. We propose that these fullerene derivatives serve as the lead compounds for a novel type of antitumor agents.

Stereochemistry of Simple Molecules inside Nanotubes and Fullerenes: Unusual Behavior of Usual Systems

“…The history of nanotubes [1,2] and fullerenes [3] spans several decades; the most important stages in understanding of their nature and properties are well represented in recent reviews and books [4][5][6][7][8][9][10]. The main directions of practical application of such nanoobjects are connected with creation of new materials [4,[7][8][9][10][11][12][13][14], applications in pharmacy and medicine [15][16][17][18][19][20][21][22][23][24] and wastewater treatment [25]. These possibilities resulted mainly from the formation of endohedral complexes of fullerenes and nanotubes; the first example, synthesis of lanthanum complexes of C 60 , was described in [26].…”

Malonic Acid-Type Fullerene Derivatives Strongly Inhibit The SARS-Cov-2 Main Protease

“…We have reported the synthesis of fullerene derivatives 1 to 4 and 8 to 13. [12,[15][16][17][18] Our previous studies con rmed that 1, 2, and 8 are trans isomers and 3 is a cis isomer. Bis-adduct fullerene derivatives such as 7 and 12 are mixtures of several regioisomers.…”

A pyridinium‑type fullerene derivative suppresses primary effusion lymphoma cell viability via the downregulation of the Wnt signaling pathway through the destabilization of β‑catenin

“…It was also found that derivative #1 suppressed PEL cell proliferation by interfering with the phosphorylation of AKT and procaspase-9 (21). Therefore, the present study focused on the cation-functionalized moiety of derivative #1 and evaluated other cationic fullerene derivatives containing pyrrolidinium, pyridinium or anilinium (derivatives #2-#9) (16,17,19,21,(23)(24)(25). All the derivatives suppressed the growth of not only PEL cell lines, but also that of KSHV-uninfected B cell lines.…”

“…Fullerene derivatives #1, #2 ( 16 , 19 , 21 ), #3 ( 23 ), #5 ( 24 , 25 ), #7 ( 24 ), #8 ( 25 ) and #9 ( 25 ) were synthesized and purified according to previously reported methods. Derivative #4 was synthesized via 1,3-dipolar cycloaddition reactions of azomethine ylide generated from 4-dimetylaminobenzaldehyde and 4-pycolylamine, followed by methylation with methyl iodide.…”

“…Since derivative #1 has a cation-functionalized moiety (pyrrolidinium) and has several beneficial biological properties, other cationic fullerene derivatives were synthesized (Fig. 1) (16,17,19,21,(23)(24)(25). In the present study, the inhibitory activities of these derivatives on PEL cell growth were analyzed and the underlying molecular mechanism(s) leading to PEL cell growth inhibition were evaluated.…”