Abstract
High efficacy and low toxicity are critical for cancer treatment. Polyoxometalates (POMs) have been reported as potential candidates for cancer therapy. On accounts of the slow clearance of POMs, leading to long-term toxicity, the clinical application of POMs in cancer treatment is restricted. To address this problem, a degradable organoimido derivative of hexamolybdate is developed by modifying it with a cleavable organic group, leading to its degradation. Of note, this derivative exhibits favourable pharmacodynamics towards human malignant glioma cell (U251), the ability to penetrate across blood brain barrier and low toxicity towards rat pheochromocytoma cell (PC12). This line of research develops an effective POM-based agent for glioblastoma inhibition and will pave a new way to construct degradable anticancer agents for clinical cancer therapy.
Highlights
In the medicinal chemistry of POMs, previous works on cancer therapy were mainly focused on the heteropolyacids, including Keggin[14,19,20,21] and Wells-Dawson[23,24,25]
The molecular structure of POM-AMB-acy has been clearly confirmed by single-crystal X-ray diffraction analysis (Fig. 2): its hexamolybdate cage is connected to the aromatic ring of 2-amino-3-methylbenzoxyl group via a Mo ≡N triple bond with the Mo1-N1 bond length of 1.735 (4) Å and the linear C1-N1-Mo1 bond angle of 176.3 (8)°, which are in great agreement with the typical organoimido groups grafted at an octahedral d0 metal center[33,38]
To prevent the side effects, this agent is endowed with degradability by introducing a cleavable functional group into its structure. This fundamental research can provide the guidance to fabricate other degradable agents based on POMs or nanoclusters for cancer therapy
Summary
In the medicinal chemistry of POMs, previous works on cancer therapy were mainly focused on the heteropolyacids, including Keggin[14,19,20,21] and Wells-Dawson[23,24,25]. We report our recent finding that a degradable organically-derivatized POM, named [Mo6O18 (≡NC6H4-2-CH3-6-CON(Cy)-CO-NH-Cy)]2− (POM-AMB-acy) (Fig. 1) can exhibit inhibitory performance towards malignant glioma cell (U251), and cross the blood brain barrier (BBB), which is the key step to develop a practical agent for glioblastoma’s treatment[39]. This compound is consisted of one hexamolybdates moiety (POM) as the efficacious center and one N-acylureido group (acy) for degradation, linked by a www.nature.com/scientificreports/. A degradable POM-based compound may be developed as a promising candidate for glioblastoma inhibition with degradability
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