Synthesis of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Cytotoxic Candidates

Abstract

Ostruthin, isolated from Paramignya trimera, was used as a scaffold to design its alkyl triphenylphosphonium derivatives. With the optimal reaction conditions in hand, five alkyl triphenylphosphonium ostruthin derivatives (1–5) were synthesized. Ostruthin and its derivatives were tested for cytotoxicity against human PANC‐1 pancreatic, Hela cervical, and HepG2 liver cancer cell lines. Ostruthin and its hexyl and heptyl triphenylphosphonium derivatives (4 and 5) showed strong preferential cytotoxicity against PANC‐1 cells with the PC50 values of 10.3 and 14.4 μM, respectively. In addition, compounds 4 and 5 also exhibited potent cytotoxicity towards HeLa cells with the IC50 values of 24.8 and 18.5 μM, respectively. The hexyl triphenylphosphonium group in 4 was found to slightly enhance cytotoxicity against HepG2 cells. Further, the morphological changes and the live‐cell imaging result suggested the anticancer potential against HeLa cells of the synthesized ostruthin derivative 5.

Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

“…Ostruthin was recently identified in an ext danum ostruthium (L.) Koch as an active constituent that inhibits TNF-α-ind reporter activity in human embryonic kidney 293 cells [16]. In the present stu uated the anti-inflammatory activities of ostruthin and its TPP derivatives w lengths of alkyl linkers in human lung adenocarcinoma A549 cells (Figure 1 obtained showed that the alkyl TPP derivatives of ostruthin exhibited anti-i activity without affecting cell viability, while ostruthin itself showed cytotox We recently reported the synthesis and biological evaluation of alkyl triphenylphosphonium (TPP) ostruthin derivatives to enhance the pharmacokinetic properties of ostruthin [17]. The modification of small molecules with TPP cations has been shown to promote mitochondrial delivery [18].…”

“…Ostruthin exhibited cytoto against human pancreatic cancer PANC-1 cells, human cervical cancer He human hepatic cancer HepG2 cells [17]. Ostruthin TPP derivatives with diff of alkyl linkers were found to exert stronger or weaker cytotoxic activities ag 1, HeLa, and HepG2 cells [17]. Collectively, these findings clearly showed t lent linking of ostruthin with a TPP moiety and alkyl linkers influenced its tivity.…”

“…Ostruthin was purified from the CHCl 3 extract of the roots of P. trimera as previously reported [11]. The TPP derivatives of ostruthin with a butyl linker (OS5), pentyl linker (OS6), hexyl linker (OS7), and heptyl linker (OS8) were prepared as described in our previous study (Figure 1) [17]. Recombinant human TNF-α was provided by Dainippon Pharmaceuticals (Osaka, Japan).…”

“…We recently reported the synthesis and biological evaluation o phenylphosphonium (TPP) ostruthin derivatives to enhance the pharmacoki ties of ostruthin [17]. The modification of small molecules with TPP catio shown to promote mitochondrial delivery [18].…”

“…The modification of small molecules with TPP cations has been shown to promote mitochondrial delivery [18]. Ostruthin exhibited cytotoxic activities against human pancreatic cancer PANC-1 cells, human cervical cancer HeLa cells, and human hepatic cancer HepG2 cells [17]. Ostruthin TPP derivatives with different lengths of alkyl linkers were found to exert stronger or weaker cytotoxic activities against PANC-1, HeLa, and HepG2 cells [17].…”