Correction: Nickel-catalyzed γ-alkylation of cyclopropyl ketones with unactivated primary alkyl chlorides: balancing reactivity and selectivity via halide exchange.

[This corrects the article DOI: 10.1039/D4RA02616K.].

Nickel-catalyzed γ-alkylation of cyclopropyl ketones with unactivated primary alkyl chlorides: balancing reactivity and selectivity via halide exchange.

A novel method was developed for synthesizing γ-alkyl ketones via nickel-catalyzed cross-electrophile coupling of cyclopropyl ketones and non-activated primary alkyl chlorides. High reactivity and selectivity can be achieved with sodium iodide as a crucial cocatalyst that generates a low concentration of alkyl iodide via halide exchange, thus avoiding the formation of alkyl dimers. This reaction possessed excellent regioselectivity and high step economy circumventing in situ or pregenerated organometallics.

Low 18F-fluorodeoxyglucose dose positron emission tomography assisted by a deep-learning image-denoising technique in patients with lymphoma.

Background: Patients with lymphoma receive multiple positron emission tomography/computed tomography (PET/CT) exams for monitoring of the therapeutic response. With PET imaging, a reduced level of injected fluorine-18 fluorodeoxyglucose ([18F]FDG) activity can be administered while maintaining the image quality. In this study, we investigated the efficacy of applying a deep learning (DL) denoising-technique on image quality and the quantification of metabolic parameters and Deauville score (DS) of a low [18F]FDG dose PET in patients with lymphoma. Methods: This study retrospectively enrolled 62 patients who underwent [18F]FDG PET scans. The low-dose (LD) data were simulated by taking a 50% duration of routine-dose (RD) PET list-mode data in the reconstruction, and a U-Net-based denoising neural network was applied to improve the images of LD PET. The visual image quality score (1 = undiagnostic, 5 = excellent) and DS were assessed in all patients by nuclear radiologists. The maximum, mean, and standard deviation (SD) of the standardized uptake value (SUV) in the liver and mediastinum were measured. In addition, lesions in some patients were segmented using a fixed threshold of 2.5, and their SUV, metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) were measured. The correlation coefficient and limits of agreement between the RD and LD group were analyzed. Results: The visual image quality of the LD group was improved compared with the RD group. The DS was similar between the RD and LD group, and the negative (DS 1-3) and positive (DS 4-5) results remained unchanged. The correlation coefficients of SUV in the liver, mediastinum, and lesions were all >0.85. The mean differences of SUVmax and SUVmean between the RD and LD groups, respectively, were 0.22 [95% confidence interval (CI): -0.19 to 0.64] and 0.02 (95% CI: -0.17 to 0.20) in the liver, 0.13 (95% CI: -0.17 to 0.42) and 0.02 (95% CI: -0.12 to 0.16) in the mediastinum, and -0.75 (95% CI: -3.42 to 1.91), and -0.13 (95% CI: -0.57 to 0.31) in lesions. The mean differences in MTV and TLG were 0.85 (95% CI: -2.27 to 3.98) and 4.06 (95% CI: -20.53 to 28.64) between the RD and LD groups. Conclusions: The DL denoising technique enables accurate tumor assessment and quantification with LD [18F]FDG PET imaging in patients with lymphoma.

Solitary bone plasmacytoma of spine with involvement of intervertebral disk: a case report and literature review.

Primary malignant bone tumors of the spine are exceedingly rare, with solitary bone plasmacytoma (SBP) representing approximately 30% of all cases. Radiological assessments are crucial for localizing SBP and for ruling out a diagnosis of multiple myeloma (MM). Imaging features resembling a "mini-brain" appear to be distinctive for SBP. Vertebral lesions accompanied by adjacent disc space involvement typically suggest spinal infections, while the potential for SBP involvement is often overlooked. We present a case of a 61-year-old female with SBP who exhibited thoraco-lumbar spine destruction and adjacent disc space involvement. The patient sought treatment at our medical center due to lumbodorsal pain radiating bilaterally to the inguinal regions. Radiological findings revealed an osteolytic lesion involving the intervertebral disc, making it challenging to distinguish between tumor and inflammation. A biopsy of the vertebral lesion confirmed the diagnosis of SBP, which was further supported by laboratory results. Post-diagnosis, the patient underwent radiotherapy, receiving a total dose of 4000 Gy, which alleviated her symptoms. We also provide a comprehensive literature review on SBP with disc involvement to aid both clinical and radiological diagnoses.

Polysaccharides from marine biological resources and their anticancer activity on breast cancer.

In recent decades, natural products from marine organisms have been widely studied for the treatment of various breast cancers. Among them, polysaccharides have been favored by researchers because of their good effects and safety. In this review, polysaccharides from marine algae including macroalgae and microalgae, chitosan, microorganisms such as marine bacteria and fungi, and starfish are addressed. Their anticancer activities on different breast cancers and action mechanisms are discussed in detail. In general, polysaccharides from marine organisms are potential sources of low side-effect and high efficiency anticancer drugs for development. However, further research on animals and clinical research are needed.

Development of a series of flurbiprofen and zaltoprofen platinum(IV) complexes with anti-metastasis competence targeting COX-2, PD-L1 and DNA.

To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues.

Evidence-based intervention on postoperative fear, compliance, and self-efficacy in elderly patients with hip fracture.

BACKGROUND: Elderly patients tend to have poor self-efficacy and poor confidence in postoperative rehabilitation for hip fractures, and are prone to negative emotions, which affect treatment compliance. AIM: To evaluate the effects of evidence-based intervention on postoperative fear, compliance, and self-efficacy in elderly patients with hip fractures. METHODS: A total of 120 patients with hip fracture surgically treated from June 2018 to June 2020 at the orthopedic department of our hospital were selected and divided into intervention and routine groups (n = 60 each) according to different nursing methods. The basic rehabilitation methods of the two groups were consistent, but patients in the intervention group received evidence-based nursing interventions at the same time. Differences between groups in the scores of motion phobia, pain fear, rehabilitation training compliance, self-efficacy, nursing satisfaction, and hip joint function were compared before and after the intervention. RESULTS: Before the intervention, there were no statistically significant differences in motion phobia and pain fear scores between the groups (all P > 0.05). However, motion phobia scores at 1 wk after intervention initiation (P < 0.05), and pain fear scores at 1 wk and 2 wk after intervention initiation (all P < 0.05), were significantly lower in the intervention group than in the routine group. On the first day of intervention, there was no significant difference in rehabilitation treatment compliance between the groups (P > 0.05); however, at 2 wk after intervention initiation, rehabilitation compliance was significantly better in the intervention group than in the routine group (P < 0.05). Before the intervention, there were no statistically significant differences in the scores for the two self-efficacy dimensions (overcoming difficulties and rehabilitation exercise self-efficacy) and the total self-efficacy score between the groups (all P > 0.05). After 2 wk of intervention, the scores for these two dimensions of self-efficacy and the total self-efficacy score were significantly higher in the intervention group than in the routine group (all P < 0.05). At 3 and 6 mo after surgery, hip function as evaluated by the Harris hip score, was significantly better in the intervention group than in the routine group (P < 0.05). Additionally, overall nursing satisfaction was significantly higher in the intervention group than in the routine group (P < 0.05). CONCLUSION: Evidence-based nursing intervention can alleviate fear of postoperative rehabilitation in elderly patients who underwent hip fracture surgery, and improve rehabilitation treatment compliance and patient self-efficacy, which promote hip function recovery.

Two Multiresponsive Luminescent Zn-MOFs for the Detection of Different Chemicals in Simulated Urine and Antibiotics/Cations/Anions in Aqueous Media.

Two Zn-MOFs, namely, {[Zn(L)0.5(bpea)]·0.5H2O·0.5DMF}n [LCU-113 (for Liaocheng University)] and {[Zn(L)0.5(ibpt)]·H2O·DMF}n (LCU-114), were synthesized based on flexible tetracarboxylic acid 1,3-bis(3,5-dicarboxyphenoxy)benzene (H4L) and different N-ligands [bpea = 1,2-dipyridyl ethane; ibpt = 3-(4'-imidazolobenzene)-5-(pyridine-4'-yl)-1,2,4-triazole]. LCU-113 and LCU-114 possess twofold interpenetrating three-dimensional pillared layer structures, in which a two-dimensional layer formed by carboxylic acid and Zn2+ ions was pillared by bpea and ibpt, respectively. The two complexes show high water stability and high luminescence sensing performance toward organic solvents, ions, and antibiotics, as well as chemicals, in simulated urine. The investigation showed that (1) LCU-113 and LCU-114 could detect uric acid (UA, 2,6,8-trihydroxypurine, metabolite of purine) and p-aminophenol (PAP, biomarker of phenamine) in simulated urine by luminescence quenching, respectively, and (2) luminescence quenching of LCU-113 and LCU-114 occurred in aqueous solutions of nitrofurazone (NZF), Fe3+, and CrO42-/Cr2O72-. All the above detections have excellent anti-interference ability and recyclability. The luminescence mechanism analysis indicates that weak interactions between the framework structures and the target analytes as well as the energy competition (inner filter effect) play an important role in sensing the above analytes. The practical application for monitoring NZF/Fe3+ in water samples was also tested.

Asymptomatic chronic suppurative cholecystitis and peritonitis mimicking metastasis by 18F-FDG PET/CT scan during sigmoid colon cancer surveillance.

The study describes an unusual case that a patient with previous history of adenocarcinoma of sigmoid colon who has developed chronic suppurative cholecystitis and peritonitis was misdiagnosed as metastasis. This case is presented to illustrate the importance of considering benign etiologies that may mimic metastatic disease when interpreting positron emmision tomography (PET)/CT scans.

Synthesis and Evaluation of Radioiodine-Labeled pH (Low) Insertion Peptide Variant 7-Like Peptide as a Noninvasive Tumor Microenvironment Imaging Agent in a Mouse MDA-MB-231 Triple-Negative Breast Cancer Model.

PURPOSE: The pH (low) insertion peptide (pHLIP) family can target the tumor microenvironment (TME). If pHLIP can be labeled with radioiodine, the imaging and treatment of tumors can be considered. However, tyrosine and tryptophan can bind with iodine in the insertion region of pHLIP, and radioiodine labeling may affect the formation of α-helix structures in acidic environments; therefore, it is necessary to adjust the structure of pHLIP. This study aims to develop an 125I-labeled pH (low) insertion peptide variant 7-like peptide (pHLIP (Var7) LP) for imaging the TME in MDA-MB-231 triple-negative breast cancer (TNBC) xenograft tumor models. PROCEDURES: Based on pHLIP (Var7), a new peptide sequence, pHLIP (Var7) LP, was obtained by the sequence modification method and then characterized. The binding of pHLIP (Var7) LP to MDA-MB-231 cells was analyzed. pHLIP (Var7) LP was labeled with 125I by the iodogen iodination method. Serial biodistribution studies and small-animal single photon emission computed tomography (SPECT)/computed tomography (CT) imaging in subcutaneous MDA-MB-231 TNBC-bearing mice were performed using [125I] I-pHLIP (Var7) LP. RESULTS: A novel peptide, pHLIP (Var7) LP, has the characteristics of an α-helix structure, electronegativity, and amphiphilicity. Circular dichroism (CD) spectroscopy showed that the peptide presented a typical pH-dependent transition from an unstructured conformation to an α-helix structure when the pH was reduced from 8.0 to 4.0. The relative fluorescence intensities of 5-carboxytetramethylrhodamine (5-TAMRA)-pHLIP(var7) LP at pH = 6.0, 6.6, and 7.4 were 100.00 ± 5.98%, 72.10 ± 4.65%, and 13.72 ± 1.41%, respectively. The distribution of [125I] I-pHLIP (Var7) LP in tumors reached the highest level (8.7 ± 1.6% ID/g) at 2 h after injection, and the tumor-to-muscle ratios and tumor-to-blood ratios increased with time. Of the measured off-target organs, the stomach, kidney, and bladder showed higher uptake levels. SPECT imaging revealed rapid and sustained tumor uptake of [125I] I-pHLIP (Var7) LP in breast cancer-bearing mice. CONCLUSIONS: This study showed that [125I]I-pHLIP (Var7)LP had rapid and sustained tumor uptake in MDA-MB-231 TNBC and provided a new method for TNBC imaging and further treatment.

The Correlation between 18F-FDG PET/CT Imaging SUVmax of Preoperative Colon Cancer Primary Lesions and Clinicopathological Factors.

BACKGROUND: The purpose of this study is to explore the correlation between the 18F-FDG PET/CT imaging maximum standardized uptake value (SUVmax) of preoperative colon cancer primary lesions and clinicopathological factors. METHODS: 88 colon cancer patients diagnosed by histopathology were collected from January 2014 to December 2015. 18F-FDG PET/CT imaging was performed before surgery. Kaplan-Meier survival analysis was used to assess the prognosis of colon cancer patients. RESULTS: The 18F-FDG PET/CT imaging SUVmax value of preoperative colon cancer primary lesion was significantly correlated with the length of the lesion, clinical stage, histopathological type, and the degree of tumor differentiation. The SUVmax value of tumors with long-diameter, ≥ 3 cm, clinically high-stage, adenocarcinoma, and poorly differentiated lesions was significantly high. In addition, the consistency between PET/CT and surgical pathological results at stage I and IV was higher. Stage II and III PET/CT are basically consistent with the pathological results of surgery. Kaplan-Meier survival analysis showed that the 5-year event-free survival rate of the SUVmax > 18.26 group was significantly lower than that of the SUVmax ≤ 18.26 group. CONCLUSION: 18F-FDG PET/CT imaging SUVmax of preoperative colon cancer primary lesions can not only reflect the proliferation and invasion ability but also monitor the recurrence and metastasis of colon cancer.

Albumin-encapsulated Nanoparticles of Naproxen Platinum(IV) Complexes with Inflammation Inhibitory Competence Displaying Effective Antitumor Activities in vitro and in vivo.

BACKGROUND: Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery. PURPOSE: The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS). METHODS: Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo. RESULTS: Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity. CONCLUSION: Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.

Design, synthesis and biological evaluation of dihydro-2-quinolone platinum(iv) hybrids as antitumor agents displaying mitochondria injury and DNA damage mechanism.

The design of novel platinum(iv) complexes with mitochondria injury competence, besides the DNA damage mechanism, is a promising way to develop new platinum drugs. Herein, dihydro-2-quinolone (DHQLO) as a mitocan was incorporated into the platinum(iv) system for the first time to prepare a new series of DHQLO platinum(iv) compounds. Complex 1b could effectively inhibit the proliferation of tumor cells in vitro and in vivo. It accumulated at higher levels in both whole cells and DNA, and easily underwent intercellular reduction to release platinum(ii) and DHQLO moieties. The released platinum(ii) complex caused serious DNA damage by covalent conjunction with the DNA duplex, and remarkably increased the expression of the γ-H2AX protein. Moreover, 1b also caused serious mitochondria injury to induce mitochondrial membrane depolarization and increase ROS generation. Such actions upon DNA and mitochondria activate the p53 apoptotic pathway synergetically in tumor cells by upregulating the protein p53 and apoptotic proteins caspase9 and caspase3, which efficiently promoted the apoptotic death of tumor cells. Compound 1b with such synergic mechanism exhibited great potential in reversing cisplatin resistance and improving antitumor efficacies.

Additional value of metabolic parameters to PET/CT-based radiomics nomogram in predicting lymphovascular invasion and outcome in lung adenocarcinoma.

PURPOSE: Lymphovascular invasion (LVI) impairs surgical outcomes in lung adenocarcinoma (LAC) patients. Preoperative prediction of LVI is challenging by using traditional clinical and imaging parameters. The purpose of this study was to investigate the value of the radiomics nomogram integrating clinical factors, CT features, and maximum standardized uptake value (SUVmax) to predict LVI and outcome in LAC and to evaluate the additional value of the SUVmax to the PET/CT-based radiomics nomogram. METHODS: A total of 272 LAC patients (87 LVI-present LACs and 185 LVI-absent LACs) with PET/CT scans were retrospectively enrolled, and 160 patients with SUVmax ≥ 2.5 of them were used for PET radiomics analysis. Clinical data and CT features were analyzed to select independent LVI predictors. The performance of the independent LVI predictors and SUVmax was evaluated. Two-dimensional (2D) and three-dimensional (3D) CT radiomics signatures (RSs) and PET-RS were constructed with the least absolute shrinkage and selection operator algorithm and radiomics scores (Rad-scores) were calculated. The radiomics nomograms, incorporating Rad-score and independent clinical and CT factors, with SUVmax (RNWS) or without SUVmax (RNWOS) were built. The performance of the models was assessed with respect to calibration, discrimination, and clinical usefulness. All the clinical, PET/CT, pathologic, therapeutic, and radiomics parameters were assessed to identify independent predictors of progression-free survival (PFS). RESULTS: CT morphology was the independent LVI predictor. SUVmax provided better discrimination capability compared with CT morphology in the training set (P < 0.001) and test set (P = 0.042). A total of 1409 CT and PET radiomics features were extracted and reduced to 8, 8, and 10 features to build the 2D CT-RS, 3D CT-RS, and the PET-RS, respectively. There was no significant difference in AUC between the 2D-RS and 3D-RS (P > 0.05), and 2D CT-RS showed a relatively higher AUC than 3D CT-RS. The CT-RS, the CT-RNWOS, and the CT-RNWS showed good discrimination in the training set (AUC [area under the curve], 0.799, 0.796, and 0.851, respectively) and the test set (AUC, 0.818, 0.822, and 0.838, respectively). There was significant difference in AUC between the CT-RNWS and CT-RNWOS (P = 0.044) in the training set. Decision curve analysis (DCA) demonstrated the CT-RNWS outperformed the CT-RS and the CT-RNWOS in terms of clinical usefulness. Furthermore, DCA showed the PETCT-RNWS provided the highest net benefit compared with the PET-RNWS and CT-RNWS. PFS was significantly different between the pathologic and RNWS-predicted LVI-present and LVI-absent patients (P < 0.001). Carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pathologic LVI, histologic subtype, and SUVmax were independent predictors of PFS in the 244 CT-RNWS-predicted cohort; and CA125, NSE, pathologic LVI, and SUVmax were the independent predictors of PFS in the 141 PETCT-RNWS-predicted cohort. CONCLUSIONS: The radiomics nomogram, incorporating Rad-score, clinical and PET/CT parameters, shows favorable predictive efficacy for LVI status in LAC. Pathologic LVI and SUVmax are associated with LAC prognosis.

Naproxen platinum(iv) hybrids inhibiting cycloxygenases and matrix metalloproteinases and causing DNA damage: synthesis and biological evaluation as antitumor agents in vitro and in vivo.

Cycloxygenases (COXs) and matrix metalloproteinases (MMPs) in the tumor microenvironment (TME) are tightly related to the progression of cancers. Here, naproxen as a potent inhibitor of both COX and MMP was combined with platinum(iv) to construct hybrids as antitumor agents. Compound 2 with comparable or even superior activities to that of cisplatin, oxaliplatin, and carboplatin, great potential for reversing drug resistance, and superior tumor targeting properties was screened out as a lead compound. Moreover, compound 2 possessed potent tumor growth inhibition capability in vivo, which was comparable to that of oxaliplatin, and displayed rather lower side effects than the platinum(ii) reference drugs. The naproxen platinum(iv) complex could easily undergo reduction and liberate the platinum(ii) complex and naproxen as well as exert a multifunctional antitumor mechanism: (i) the liberated platinum(ii) fragment would cause serious DNA injury; (ii) naproxen would inhibit COX-2 and decrease tumor-associated inflammation; and (iii) the naproxen platinum(iv) complex exhibited remarkable MMP-9 inhibition in tumor tissues. These antitumor functions can help reduce the growth and metastasis of malignancy.

A potent aminonaphthalimide platinum(IV) complex with effective antitumor activities in vitro and in vivo displaying dual DNA damage effects on tumor cells.

A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9.

Synthesis and evaluation of bi-functional 7-hydroxycoumarin platinum(IV) complexes as antitumor agents.

A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. By a unique mechanism, the 7-hydroxycoumarin platinum(IV) complex attacks DNA via the released platinum(II) compound, meanwhile it also inhibits the activities of cyclooxygenase by coumarin fragment. This action mechanism might be of much benefit for reducing tumor-related inflammation in the progress of inhibiting tumor proliferation and overcoming cisplatin resistance. The incorporation of 7-hydroxycoumarin leads to significantly enhanced platinum accumulation in both whole tumor cells and DNA. The HSA interaction investigation reveals that the tested coumarin platinum(IV) compound could effectively combine with HSA via van der Waals force and hydrogen bond.

Development of a series of 4-hydroxycoumarin platinum(IV) hybrids as antitumor agents: Synthesis, biological evaluation and action mechanism investigation.

A series of new 4-hydroxycoumarin platinum(IV) complexes were designed, synthesized and evaluated as antitumor agents. All the title compounds display moderate to effective antitumor activities toward the tested cell lines and two prominent compounds were screened out with activities comparable to cisplatin and oxaliplatin. The mechanism investigation demonstrates that the platinum(IV) compounds could be reduced to bivalence and exert significant genotoxicity to tumor cells. Meanwhile the coumarin moiety endows the title compounds with cyclooxygenase inhibitory competence which might favour the reduction of tumor-related inflammation and further influence tumor proliferation. The coumarin platinum(IV) complex could effectively induce apoptosis of SKOV-3 cells through up-regulating the expression of caspase3 and caspase9. Furthermore, the conversion of platinum(II) drugs to platinum(IV) form via the conjunction with 4-hydroxycoumarin enhances the drug uptake in whole cells and DNA simultaneously. Moreover, the 4-hydroxycoumarin platinum(IV) complex could combine with human serum albumin via van der Waals force and hydrogen bond, which would influence their transport and bioactivities in vivo.

Design and synthesis of a new series of low toxic naphthalimide platinum(IV) antitumor complexes with dual DNA damage mechanism.

Naphthalimide platinum(IV) antitumor complexes with potential dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The incorporation of DNA targeted naphthalimide group to the platinum(IV) system exerts much positive impacts on their antitumor efficacy. The mechanism research reveals that the title compounds could interact with dsDNA in platinum(IV) form via the naphthalimide group and cause DNA lesion. The further reduction would release platinum(II) complexes and naphthalimide acids which would induce remarkable secondary damage to DNA. Furthermore, the naphthalimide platinum(IV) compounds could combine with human serum albumin via electrostatic force, which are favourable for their storage and transport in blood. Moreover, the title compounds exhibit higher accumulation in tumor cells, and exert lower toxic and higher safe properties than oxaliplatin in vivo.