Background: The single-agent therapy was unable to provide an effective control of the
malignant process, a well-established strategy to improve the efficacy of antitumor therapy is the
rational design of drug combinations aimed at achieving synergistic effects.
Objective: The objective of this study is generating the new potential anticancer agents with
synergistic activity. Owing to the unique mechanism of action of Camptothecin (CPT), it has shown
abroad spectrum of anti-cancer activity against human malignancies, and growing evidence revealed
that Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) reduce the risk of different kinds of cancers.
So four CPT-NSAIDs conjugates were synthesized and evaluated.
Methods: In this study, a series of novel CPT - NSAIDs derivatives were synthesized by
esterification. These new compounds were evaluated for in vitro antitumor activity against tumor
cell lines A549, Hela, HepG2, HCT116 by MTT assay. To probe the required stabilities as prodrugs,
stability tests were studied in human plasma. To further evaluate the stability of Ketoprofen-CPT
in vivo, the female SD rats were used to determine the pharmacokinetics following a single oral dose.
Results: In vitro results showed that Ketoprofen-CPT and Naproxen-CPT conjugates possessed nice
efficacy. In a molecular docking model, the two conjugates interacted with Topo I-DNA through
hydrogen bonds, - stacking and so on.In human plasma results showed that the prodrug
was converted to ketoprofen and another compound. The female SD rats were used to determine the
pharmacokinetics following a single oral dose, the half-life (t1/2) of Ketoprofen-CPT was
approximately 12 h which was much longer than that of CPT.
Conclusion: Good activity was noted for some compounds will be helpful for the design of dualaction
agents with most promising anti-cancer activity.