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A convenient method has been developed for the glycol-conjugation in 3-position of β-anhydroicaritine in a reasonable yield. The structure of the 3-glycosylated β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Keywords: imidazopyridine; cycloaddition; 2-aminopyridine; chromones; DTBP EN imidazopyridine cycloaddition 2-aminopyridine chromones DTBP 2570 2580 11 07/31/23 20230817 NES 230817 Graph Imidazopyridines are an important class of aza-fused heterocycles in the pharmaceutical industry, and they exhibit wide biological activities, Including, anticancer [1] and antibacterial [6] action, central nervous system modulation, [9] and kinase inhibition. HRMS (ESI+): I m i / I z i [M + H] SP + sp calcd for [C SB 14 sb H SB 10 sb BrN SB 2 sb O SB 2 sb ] SP + sp : 316.9920; found: 316.9923. For a proof of concept, we described a novel and facile I SB 2 sb /DTBP promoted synthesis of C3-carbonylated imidazopyridines from chromones and 2-aminopyridines via ring opening (3+2) cycloaddition by employing simple and readily available starting materials. [Extracted from the article]

Camptothecin (CPT) is an important natural product targeting to Topoisomerase I (Topo I). Despite the high antitumor activity, this compound cannot enter clinical trial owing to its high toxicity and low bio‐availability. In this project, the ring‐closing metathesis (RCM) synthesis strategy was employed to introduce spirocycle functional group in the 5‐position of CPT. Thus, in the catalysis of Grubbs II catalyst, 5,5‐diallylcamptothecin underwent RCM reaction to give 5‐spirocycle CPT compound in 73% yield. [ABSTRACT FROM AUTHOR]

Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1HNMR, 13CNMR and MS spectrum. The results showed that compounds 6e, 6g, 6j, 6l, 6m, 6b, 6e, 6i, and 6n showed high cytotoxicity to HepG2 and compounds 6b, 6e-g, 6l, 6n, 7b, 7d, 7h, 7i, 7n, 8g, 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b, 6e, 6g, and 6k, the other compounds showed less toxic to LO2 at a concentration of 50 μg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages. [ABSTRACT FROM AUTHOR]

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of β-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A novel method for synthesizing α-aminoalkyl phosphine oxides in aqueous medium, using Ar 2 P(O)-H reagents, alcohols and amines, is described. This method: (i) allows for the smooth aminophosphinoylation of alcohols with amines and H-phosphine oxides under mild conditions; (ii) provides an efficient and alternative approach to access various α-aminoalkylphosphine oxides. Although various amines exhibited remarkable versatility and tolerance for functional groups in this reaction, alcohols and H-phosphine oxides demonstrated limited applicability as reactants. Hence, further investigation using a wider range of substrates is crucial. The postulated mechanism indicated that the three-component reaction followed the imine pathway due to the in situ oxidation of alcohol to aldehyde.

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.