Dual-targeting antitumor conjugates derived from platinum(IV) prodrugs and microtubule inhibitor CA-4 significantly exhibited potent ability to overcome cisplatin resistance

Huang, Xiaochao; Wang, Meng; Wang, Chun-Gu; Hu, Weiwei; Qin, You; Yang, Yong; Yu, Chunhao; Liao, Zhi‐Xin; Gou, Shaohua; Wang, Hengshan

doi:10.1016/j.bioorg.2019.103236

Cited by 29 publications

(15 citation statements)

References 42 publications

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“…Modification results in formation of a variety of Pt(IV) prodrugs that on their own [2,28,29], even before attachment to carriers, might improve pharmacological activity compared to platinum (II) systems used currently. They show kinetic inertness that makes them more stable in blood circulation and are activated via intracellular reduction to square planar platinum(II) compounds after cellular uptake [30][31][32][33].…”

Section: Platinum Drugs Conjugatesmentioning

confidence: 99%

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Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

Piorecka

Kurjata

Stańczyk

2021

IJMS

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The development in the area of novel anticancer prodrugs (conjugates and complexes) has attracted growing attention from many research groups. The dangerous side effects of currently used anticancer drugs, including cisplatin and other platinum based drugs, as well their systemic toxicity is a driving force for intensive search and presents a safer way in delivery platform of active molecules. Silicon based nanocarriers play an important role in achieving the goal of synthesis of the more effective prodrugs. It is worth to underline that silicon based platform including silica and silsesquioxane nanocarriers offers higher stability, biocompatibility of such the materials and pro-longed release of active platinum drugs. Silicon nanomaterials themselves are well-known for improving drug delivery, being themselves non-toxic, and versatile, and tailored surface chemistry. This review summarizes the current state-of-the-art within constructs of silicon-containing nano-carriers conjugated and complexed with platinum based drugs. Contrary to a number of other reviews, it stresses the role of nano-chemistry as a primary tool in the development of novel prodrugs.

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Section: Platinum Drugs Conjugatesmentioning

confidence: 99%

“…Figure32. Synthesis of cisplatin-collagen "intelligent" MSN and its action towards normal and cancer cells (A549)[97].…”

mentioning

confidence: 99%

Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

Piorecka

Kurjata

Stańczyk

2021

IJMS

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“…Then cells were treated with different doses of 7j (0, 2, 4 and 8 µM) for 24 h. After treatment, cells were treated with 5 µM cationic dye JC-1 (KGA601, Nanjing KeyGEN Biotech, Nanjing, China) for 30 min. Finally, cells were harvested and washed with PBS, and then analyzed by flow cytometer (BD Biosciences, San Jose, CA, USA) [42].…”

Section: Analysis Of Mitochondrial Membrane Potentialmentioning

confidence: 99%

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Wang

et al. 2020

Molecules

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A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

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“…The linkers were conjugated to CA4 by stable ether or ester linkages (Figure ). − The bonds between the linker and CA4 are fairly stable under physiological conditions, suggesting that following reduction the linker is likely to remain tethered to CA4 and that the released bioactive agent is the CA4-linker conjugate rather than free CA4.…”

Section: Introductionmentioning

confidence: 99%

“…Pt(IV) complexes that were tethered to the axial OH with linkers that are not likely to release the free CA4 following reduction. − …”

Section: Introductionmentioning

confidence: 99%

Are Pt(IV) Prodrugs That Release Combretastatin A4 True Multi-action Prodrugs?

et al. 2021

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Metrics & MoreArticle Recommendations * sı Supporting Information ABSTRACT: "Multi-action" Pt(IV) derivatives of cisplatin with combretastatin A4 (CA4) bioactive ligands that are conjugated to Pt(IV) by carbonate are unique because the ligand (IC 50 < 10 nM) is dramatically 1000-folds more cytotoxic than cisplatin in vitro. The Pt(IV)-CA4 prodrugs were as cytotoxic as CA4 itself, indicating that the platinum moiety probably plays an insignificant role in triggering cytotoxicity, suggesting that the Pt(IV)-CA4 complexes act as prodrugs for CA4 rather than as true multi-action prodrugs. In vivo tests (Lewis lung carcinoma) show that ctc-[Pt(NH 3 ) 2 (PhB)(CA4)Cl 2 ] inhibited tumor growth by 93% compared to CA4 (67%), cisplatin (84%), and 1:1:1 cisplatin/CA4/PhB (85%) while displaying <5% body weight loss compared to cisplatin (20%) or CA4 (10%). In this case, and perhaps with other extremely potent bioactive ligands, platinum(IV) acts merely as a self-immolative carrier triggered by reduction in the cancer cell with only a minor contribution to cytotoxicity.

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Dual-targeting antitumor conjugates derived from platinum(IV) prodrugs and microtubule inhibitor CA-4 significantly exhibited potent ability to overcome cisplatin resistance

Cited by 29 publications

References 42 publications

Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Are Pt(IV) Prodrugs That Release Combretastatin A4 True Multi-action Prodrugs?

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