20-esterification of 5-spiro CPT and their anticancer activity in vitro.

20-ester of 5-spirocycle campthothecin derivatives were successfully constructed and synthesised by Steglich esterification in a moderate yield. These derivatives showed a better solubility. Compared to parent compound, most of these 20-ester-5-spirocycle campthothecin derivatives (besides 3g) showed a better inhibition activity against HepG2 cell line.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

Synthesis of 3- and 5-ß-anhydroicaritine norcantharidin conjugates.

Using molecular hybridisation to develop conjugates of natural antitumor drugs is one of the research hotspots in recent drug development. In this study, ß-anhydroicaritine with anticancer activity was conjugated to norcantharidine selectively to develop new antitumor lead candidates. In the condition of EDCI/DMAP/DCM, the C-3 and C-5 hydroxyl groups of ß-anhydroicaritine was coupled with norcantharidin monoacid ester respectively, and the inhibitory activity of the synthesised conjugates against HepG2, MCF-7 and L-02 cells were tested by CCK-8 method. Most of these conjugates showed a better activity against HepG2 and MCF-7 cell lines compared to parent compound icaritin, but weaker than another parent compound norcantharidin.

Glyco-conjugation in 3-ß-anhydroicaritine.

A convenient method has been developed for the glycol-conjugation in 3-position of ß-anhydroicaritine in a reasonable yield. The structure of the 3-glycosylated ß-anhydroicaritine derivatives was confirmed to be correct by 1H NMR, 13C NMR and HRMS spectrum. These compounds are less soluble than icaritin, but more soluble than icariside II in CCl4. The screening results showed that compounds 12h, 12i and 12j had higher cytotoxicity to HepG2 and MCF-7 at a concentration of 50 µM.

Regio-selective synthesis and activity research on 7-icaritin norcantharidin conjugates.

Due to complexity of tumor diseases and resistance of targeted drug, targeted drug usually cannot meet the needs of cancer treatment. Therefore, the conjugate constructed by two anticancer agents maybe a better solution for the tumor diseases. As natural anticancer agents, icaritin and norcantharidin are selected for the construction of conjugate. In the condition of EDCI/DMAP, icaritin is reacted with norcantharidin esters to give the desired 7-esters selectively in a moderate yield. MTT method was used to test the cytotoxicity and intensity on Hep G2 and MCF-7 in vitro. Some of the compounds (4a, 4i and 4j) show a better inhibition against Hep G2 and MCF-7 cell lines in vitro, and are deserved to be a potential drug candidate to develop in vivo.

Selective alkylation of ß-anhydroicaritine and their biological evaluation on anticancer.

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of ß-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated ß-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen.

Synthesis of ring opening of evodiamine derivatives and evaluation on their biological activity.

As a main bioactive component extracted from Evodiae fructus, evodiamine has a variety of pharmacological activities. In this paper, evodiamine was chosen as starting material to react with different halides. Upon treatment of TFA, a series of novel ring-opening evodiamine derivatives 3a-o were successfully synthesized in a moderate to high yields. These obtained compounds exhibit a moderate to good antitumor activity against BGC803 and SW480 in vitro test by MTT assay. The results showed that hexyl substituted evodiamine derivative (3j, R=hexyl) has a strong antitumor activity against BGC803 and SW480.

Synthesis and biological evaluation of camptothecin substituted norcantharimide derivatives.

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803.

A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.

A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I. The total yield can reach 71%. This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues. The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.