Super-high procoagulant activity of gecko thrombin: A gift from sky dragon.

AIMS: Gecko, the "sky dragon" named by Traditional Chinese Medicine, undergoes rapid coagulation and scarless regeneration following tail amputation in the natural ecology, providing a perfect opportunity to develop the efficient and safe drug for blood clotting. Here, gecko thrombin (gthrombin) was recombinantly prepared and comparatively studied on its procoagulant activity. METHODS: The 3D structure of gthrombin was constructed using the homology modeling method of I-TASSER. The active gthrombin was prepared by the expression of gecko prethrombin-2 in 293 T cells, followed by purification with Ni2+ -chelating column chromatography prior to activation by snake venom-derived Ecarin. The enzymatic activities of gthrombin were assayed by hydrolysis of synthetic substrate S-2238 and the fibrinogen clotting. The vulnerable nerve cells were used to evaluate the toxicity of gthrombin at molecular and cellular levels. RESULTS: The active recombinant gthrombin showed super-high catalytic and fibrinogenolytic efficiency than those of human under different temperatures and pH conditions. In addition, gthrombin made nontoxic effects on the central nerve cells including neurons, contrary to those of mammalian counterparts, which contribute to neuronal damage, astrogliosis, and demyelination. CONCLUSIONS: A super-high activity but safe procoagulant candidate drug was identified from reptiles, which provided a promising perspective for clinical application in rapid blood clotting.

A rapid classification method of tea products utilizing X-ray photoelectron spectroscopy: Relationship derived from correlation analysis, modeling, and quantum chemical calculation.

The classification of tea products is nowadays mainly determined by sensory assessment and chemical analysis methods. These methods are subjective, time-consuming, and laborious. In this work, a rapid analytical method for tea classification was proposed on the basis of X-ray photoelectron spectroscopy (XPS) and quantum chemical calculation. A total of 56 kinds of tea products were studied. By utilizing the data fusion strategy, the correlation between XPS peak parameters and tea characteristics was established. The quantum chemical calculations of the core-level ionization potentials deepen the understanding of the XPS features. The binding energy of the main fitted peak for O 1s, BE1O1s, was found to have a good correlation with tea polyphenols contents, which can be used to classify tea products into six tea types (black, dark, green, oolong, white, and yellow tea) with an accuracy greater than 90 %. The results suggest that the proposed XPS method is suitable for the rapid discrimination of tea classification, which contributes to the efficient application of tea.

Tai Chi Quan Versus Physical Therapy on Pain and Cognitive Performance for Elderly People With Chronic Low Back Pain: Study Protocol for a Randomized Controlled Trial.

Objectives: Chronic low back pain has become a major cause of global disability and caused a huge economic burden to society. Physical therapy is a vital strategy for rehabilitation of chronic low back pain. Although several trials have shown that Tai Chi Quan is a beneficial treatment, the comparative effectiveness of Tai Chi Quan versus physical therapy is unknown. We are conducting a randomized controlled trial to assess the effectiveness of Tai Chi Quan versus that of physical therapy in treating chronic low back pain. Methods: We will perform a single-blind randomized controlled trial on elderly people with chronic low back pain. 138 participants will be randomly assigned to the Tai Chi Quan group (60-min classes, three times per week for 12 weeks) or physical therapy group (10 min of evaluation and warm-up, 40 min of therapist-directed exercise therapy, and 10 min of relaxation, three times per week for 12 weeks) with an allocation of 1:1. The participants will be followed up for 40 weeks for the study of long-term effects. The primary outcomes include pain intensity and back-related function at 12 weeks. Secondary outcomes include lumbar quantitative sensory testing, balance, cognitive function, psychosocial function, cost-effectiveness, compliance and adverse events. We will perform the intention-to-treat analysis for withdrawal and missing data. Discussion: The study will be the first randomized trial with comparative-effectiveness of Tai Chi Quan and physical therapy for chronic low back pain. Standardized protocol, large sample size, and comprehensive outcomes are important features in this trial. This study aims to determine the feasibility and effectiveness of Tai Chi Quan for low back pain. The results of this study will be beneficial for elderly people with low back pain and medical rehabilitation personnel. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2000029723.

Expression of Mir-489-3p as an Effective Marker of Poor Prognosis in Patients with Non-small-cell Lung Carcinoma.

Context: Lung carcinoma accounts for the majority of cancer deaths, and its 5-year survival rate isn't optimistic. Remarkable progress has been made in recent decades toward understanding the biological behavior of non-small-cell lung carcinoma (NSCLC) and creating targeted molecular therapies for diagnosis and treatment. However, little literature is available on the topic, and the clinical significance and application of miR-489-3p for NSCLC can't yet be determined. Objective: The study intended to determine if miR-489-3p can predict prognosis for patients with NSCLC. Design: The research team designed a prospective study to examine in depth and analyze the molecular science of NSCLC tumors in a clinical setting. Setting: The study took place in the Department of the Special Ward at the Shanxi Provincial Cancer Hospital in Taiyuan, Shanxi, China. Participants: Participants were 116 patients with NSCLC at the hospital and 87 healthy people. Outcome Measures: A type of microRNA (miRNA), MiR-489-3p, was detected using nano-polymerase chain reaction (PCR). The diagnostic value of miR-489-3p for lung carcinoma and its predictive value for death from the disease were analyzed using a receiver operating characteristic (ROC) curve, and the three-year prognosis for patients was examined. Human NSCLC cell lines and normal, human, lung epithelial cells were obtained, and miR-489-3p was detected to assess the biological effects on lung-cancer cells. Results: MiR-489-3p has low expression in lung-cancer tissues, which indicates its good predictive value for prognosis for and death of lung-cancer patients. The activity of tumor cells increased after the inhibition of miR-489-3p. Conclusions: A low level of miR-489-3p indicates a poor prognosis for patients with NSCLC. A deeper understanding of the mechanism of miR-489-3p in lung carcinoma may be the key to the earlier diagnosis and treatment of lung carcinoma.

The Skin-Sparing Debridement Technique in Necrotizing Soft-Tissue Infections: A Systematic Review.

BACKGROUND: Skin-sparing debridement (SSd) was introduced as an alternative to en bloc debridement (EBd) to decrease morbidity caused by scars in patients surviving Necrotizing soft-tissue infections (NSTI). An overview of potential advantages and disadvantages is needed. The aim of this review was to assess (1) whether SSd is noninferior to EBd regarding general outcomes, that is, mortality, length of stay (LOS), complications, and (2) if SSd does indeed result in decreased skin defects. METHODS: A systematic literature search was performed according to the PRISMA guidelines. All human studies describing patients treated with SSd were included, when at least of evidence level consecutive case series. Studies describing up to 20 patients were pooled to improve readability and prevent overemphasis of findings from single small studies. RESULTS: Ten studies, one cohort study and nine case series, all classified as poor based on Chambers criteria for case series, were included. Compared to patients treated with EBd, patients treated with SSd had no increased mortality rate, LOS or complication rate. SSd-treated patients had a high rate (75%) of total delayed primary closure (DPC) in the pooled case series. CONCLUSION: The current available evidence is of insufficient quality to conclude whether SSd is noninferior to EBd for all assessed outcomes. There are suggestions that SSd may result in a decreased need for skin transplants, which could potentially improve the (health related) quality of life in survivors. Experienced surgical teams could cautiously implement SSd under close monitoring, ideally with uniform outcome registry.

Efficacy and safety of acupuncture in patients with cancer-related fatigue: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer-related fatigue (CRF) is considered a common complication of cancer or cancer treatment, which has a serious adverse effect on the life and of cancer patients, leading to a decline in their quality of life (QoL). The existing clinical trials revealed that acupuncture has a positive effect on CRF, and there are fewer adverse events confirmed in the corresponding systematic review. However, in recent years, new studies on using acupuncture to treat CRF were conducted, so in order to evaluate its efficacy, an updated systematic review. This protocol provides research methods for systematic review and meta-analysis of the safety and effectiveness of acupuncture for the treatment of CRF. METHODS: We will searched the randomized controlled trial literature of acupuncture treatment for CRF in 4 English and 4 Chinese databases, including PubMed, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (Central), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database(CBM), China Science Journal Database (VIP), and Wanfang Database. Simultaneously, other resources are manually retrieved which include reference lists of identified publications, conference articles, and grey literature. We also included the clinical randomized controlled trials of acupuncture treatment for CRF in the study. The search language is limited to Chinese and English. Two trained reviewers independently completed research screening, data extraction, and research quality assessment. RevMan (V.5.3) software was used to perform data statistical analysis and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. RESULTS: This study is based on past and present clinical evidence to comprehensively evaluate the effectiveness and safety of acupuncture treatment for CRF. CONCLUSION: Through this systematic review, we will provide the latest high-quality evidence of whether acupuncture treatment for CRF is effective and safe and also provide a theoretical basis for clinicians to choose acupuncture for the treatment of CRF. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202090049.

Imperatorin and ß-sitosterol have synergistic activities in alleviating collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic disease with complex molecular network of pathophysiology, single drug is usually not full satisfactory because it is almost impossible to target the whole molecular network of the disease. Drug combinations that act synergistically with each another is an effective strategy in RA therapy. In this study, we aimed to establish a new strategy to search effective synergized compounds from Chinese herbal medicine (CHM) used in RA. Based on multi-information integrative approaches, imperatorin (IMP) and ß-sitosterol (STO) were predicted as the most effective pair for RA therapy. Further animal experiments demonstrated that IMP+STO treatment ameliorated arthritis severity of collagen-induced arthritis (CIA) rats in a synergistic manner, whereas IMP or STO administration separately had no such effect. RNA sequencing and IPA analysis revealed that the synergistic mechanism of IMP+STO treatment was related to its regulatory effect on 5 canonical signaling pathways, which were not found when IMP or STO used alone. Moreover, LTA, CD83, and SREBF1 were 3 important targets for synergistic mechanism of IMP+STO treatment. The levels of these 3 genes were significantly up-regulated in IMP+STO group compared to model group, whereas IMP or STO administration separately had no effect on them. In conclusion, this study found that IMP and STO were 2 synergistic compounds from the CHM in RA therapy, whose synergistic mechanism was closely related to regulate the levels of LTA, CD83, and SREBF1.

[Progress of the mechanism research of acupuncture in treatment of diet-induced obesity].

The literature of experimental research on diet-induced obesity treated with acupuncture was retrieved. The aspects of epigenetics, neuroendocrine system, intestinal flora, inflammatory response, oxidative stress and substance metabolism of the mechanism of acupuncture in the treatment of diet-induced obesity were summarized. It is suggested that the potential mechanism of acupuncture in the treatment of diet-induced obesity should be discussed in the aspects of the interaction of Toll-like receptors on obesity-intestinal flora-immune function, the improvement of insulin resistance, epigenetics and antioxidant stress.

Electroacupuncture promotes regeneration and repair of myelin sheath of corpus callosum in demyelination mice / 针刺研究

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in accelerating the aggregation of microglia and promoting the remyelination at the location of demyelination. METHODS: C57BL/6 mice were randomly divided into 4 groups: normal, control, model (LPC) and LPC＋EA. The demyelination model was established by microinjection of Lysolecithin (LPC, 1 µL) into the left corpus callosum. EA (2 Hz/15 Hz, 2－4 mA) was applied to "Baihui"(GV20)and "Zhiyang"(GV9)for 30 min，once daily for 3 days, then, once every other day for 18 days. Immuno-fluorescence staining was used to observe the expression of myelin basic protein (MBP) and Axl tyrosine kinase receptor (Axl), Iba1 and numbers of Olig2-positive oligodendrocytes in the corpus callosum. Western blot was employed to detect the expression of MBP in the corpus callosum, and Oil Red O staining was used to observe changes of number of myelin pieces. RESULTS: Following modeling, the expression levels of MBP on day 5 and 10 after modeling were significantly decreased (P<0.05, P<0.01), Iba1 expression and Olig2-positive oligodendrocyte numbers on day 10 apparently increased (P<0.001, P<0.01). On day 21 after modeling, the levels of the above mentioned indexes returned to normal. After EA intervention, the levels of MBP expression on day 5 and 10, Axl, Iba1 protein expression and Olig2-positive oligodendrocyte numbers on day 5 were markedly increased (P<0.001，P<0.01，P<0.05), while Iba1 expression on day 10 was considerably decreased in comparison with the model group (P<0.01)．Oil Red O staining showed that on day 5 after modeling, the number of red lipid droplets were obviously increased in the corpus callosum tissue on the injection side, and apparently reduced in the EA group, suggesting a clearance of the accumulated myelin fragments by EA. CONCLUSION: EA intervention may reduce myelin debris and promote the aggregation of microglial cells and oligodendrocytes to the injured site, accelerate the myelin regeneration and up-regulate the expression of MBP and Axl of corpus callosum in demyelination mice.

[Efficacy of acupuncture combined with hydro-acupuncture for transverse processes syndrome of the third lumbar vertebra].

OBJECTIVE: To observe the clinical efficacy differences between acupuncture combined with hydro-acupuncture and acupuncture alone for transverse processes syndrome of the third lumbar vertebra. METHODS: One hundred patients were randomly divided into an observation group and a control group, 50 cases in each one. The patients in the control group were treated with regular acupuncture at Weizhong (BL 40), ashi points, Jiaji (L2～L4) and Shenshu (BL 23); the acupuncture was given once a day, six treatments per week for consecutive 2 weeks. Based on the acupuncture treatment in the control group, in the observation group the No.5 injection needle was applied to relieve the tenderness points on the transverse process and articular process of the third lumbar vertebra, followed by hydro-acupuncture with Danshen injection (1 mL per point, 7 days per injection for 2 weeks). The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) scale and Oswestry disability index (ODI) were observed before treatment, after treatment and during six-month follow-up visit in the two groups. In addition, the clinical efficacy was compared between the two groups. RESULTS: Forty-eight patients completed treatment and 2 patients dropped off in the observation group, while 47 patients completed treatment and 3 patients dropped off in the control group. The total effective rate was 91.7% (44/48) in the observation group, which was significantly superior to 76.6% (36/47) in the control group (P<0.05). Compared before treatment, the VAS and ODI in the two groups were reduced after treatment and during six-month follow-up visit, while the JOA was increased (all P<0.05); the VAS and ODI in the observation group was lower than that in the control group, while JOA in the observation group was higher than that in the control group (all P<0.05). CONCLUSION: Acupuncture combined with hydro-acupuncture are effective for transverse processes syndrome of the third lumbar vertebra, and could significantly improve lumbar function and relieve the pain symptoms, which is superior to regular acupuncture.

Zhuang Gu Guan Jie Wan: Reasonable Application Can Alleviate the Liver Injury for Osteoarthritis Treatment.

The potential toxicity of herbal drugs, particularly drug-induced liver injury (DILI), has received extensive attention as the use of Chinese herbal medicine has rapidly increased globally. As a classic Chinese patent medicine, Zhuang Gu Guan Jie Wan (ZGGJW) has been brought into focus recently because of its satisfactory therapeutic effects on osteoarthritis (OA) as well as its unanticipated side effects. This study aimed to decipher the puzzling phenomenon of liver injury developing in response to ZGGJW that varies by the subtype of OA. Normal, anterior cruciate ligament transaction (ACLT) and partial medial meniscectomy (MMx) induced OA and ovariectomy combined with ACLT and partial MMx induced rat models were used and treated orally with ZGGJW or distilled water for 30 days. The results from histopathology, biochemistry, and immunohistochemistry showed that ZGGJW induced liver injury, increased the level of malondialdehyde (MDA), and decreased the levels of total antioxidation capability (T-AOC), superoxide dismutase (SOD), interleukin-22 (IL-22), and signal transducer and activator of transcription factor 3 (STAT3) in the liver of normal rats, while liver injury was alleviated and showed different tendencies in the above markers for ACLT and partial MMx induction rats and ovariectomy combined with ACLT and partial MMx induction rats after ZGGJW treatment. In the OA disease states, hepatic injury induced by ZGGJW could be associated with an impairment in antioxidant capacity and the high levels of IL-22 and STAT3 after ZGGJW treatment may be responsible for the slight hepatic injury of ZGGJW based on the subtype of OA. This study provides a novel approach to better understanding of the risks and limitations when using potentially toxic Chinese patent medicine in clinical applications.

Hei-Gu-Teng Zhuifenghuoluo Granule Modulates IL-12 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) like Tripterygium wilfordii Hook. F. or Sinomenium acutum (Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which contains Periploca forrestii Schltr., Sinomenium acutum (Thunb.) Rehd et Wils., and Lysimachia paridiformis Franch. var. stenophylla Franch. was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis with in vivo and in vitro experiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice model in vivo and U937 cell model in vitro. The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger. In vivo experiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway. In vitro experiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.

Therapeutic Potential of Pien Tze Huang on Experimental Autoimmune Encephalomyelitis Rat.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is still lack of commercially viable treatment currently. Pien Tze Huang (PZH), a traditional Chinese medicine, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects. This study investigated the possible therapeutic effects of PZH on experimental autoimmune encephalomyelitis (EAE) rats, a classic animal model of MS. Male Lewis rats were immunized with myelin basic protein (MBP) peptide to establish an EAE model and then treated with three doses of PZH. Clinical symptoms, organ coefficient, histopathological features, levels of proinflammatory cytokines, and chemokines as well as MBP and Olig2 were analyzed. The results indicated that PZH ameliorated the clinical severity of EAE rats. It also remarkably reduced inflammatory cell infiltration in the CNS of EAE rats. Furthermore, the levels of IL-17A, IL-23, CCL3, and CCL5 in serum and the CNS were significantly decreased; the p-P65 and p-STAT3 levels were also downregulated in the CNS, while MBP and Olig2 in the CNS of EAE rats had a distinct improvement after PZH treatment. In addition, PZH has no obvious toxicity at the concentration of 0.486 g/kg/d. This study demonstrated that PZH could be used to treat MS.

The Effect of Triptolide in Rheumatoid Arthritis: From Basic Research towards Clinical Translation.

Triptolide (TP), a major extract of the herb Tripterygium wilfordii Hook F (TWHF), has been shown to exert potent pharmacological effects, especially an immunosuppressive effect in the treatment of rheumatoid arthritis (RA). However, its multiorgan toxicity prevents it from being widely used in clinical practice. Recently, several attempts are being performed to reduce TP toxicity. In this review, recent progress in the use of TP for RA, including its pharmacological effects and toxicity, is summarized. Meanwhile, strategies relying on chemical structural modifications, innovative delivery systems, and drug combinations to alleviate the disadvantages of TP are also reviewed. Furthermore, we also discuss the challenges and perspectives in their clinical translation.

Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-γ Pathway.

Cervical spondylotic radiculopathy (CSR) is the most general form of spinal degenerative disease and is characterized by pain and numbness of the neck and arm. Gentongping (GTP) granule, as a classical Chinese patent medicine, has been widely used in curing CSR, whereas the underlying mechanism remains unclear. Therefore, the aim of this study is to explore the pharmacological mechanisms of GTP on CSR. The rat model of CSR was induced by spinal cord injury (SCI). Our results showed that GTP could significantly alleviate spontaneous pain as well as ameliorate gait. The HE staining and Western blot results showed that GTP could increase the quantity of motoneuron and enhance the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) in the spinal cord tissues. Meanwhile, immunofluorescence staining analysis indicated that GTP could reduce the expression of TNF-α in the spinal cord tissues. Furthermore, the protein level of Bax was decreased whereas the protein levels of Bcl-2 and NF200 were increased after the GTP treatment. These findings demonstrated that GTP might modulate the PPAR-γ pathway by inhibiting the inflammatory response and apoptosis as well as by protecting the cytoskeletal integrity of the spinal cord, ultimately play a neuroprotective role in CSR.

Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice.

Yupingfeng San (YPFS) is a representative Traditional Chinese Medicine (TCM) formula with accepted therapeutic effect on Asthma. However, its action mechanism is still obscure. In this study, we used network pharmacology to explore potential mechanism of YPFS on asthma. Nucleotide-binding oligomerization domain (NOD)-like receptor pathway was shown to be the top one shared signaling pathway associated with both YPFS and asthma. In addition, NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome was treated as target protein in the process of YPFS regulating asthma. Further, experimental validation was done by using LPS-stimulated U937 cells and ovalbumin (OVA)-sensitized BALB/c mice model. In vitro experiments showed that YPFS significantly decreased the production of TNF-α and IL-6, as well as both mRNA and protein levels of IL-1ß, NLRP3, Caspase-1 and ASC in LPS-stimulated U937 cells. In vivo experiment indicated that YPFS treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. Moreover, YPFS treatment remarkably decreased the mRNA and protein levels of IL-1ß, NLRP3, Caspase-1 and ASC in lung tissue of asthmatic mice. In conclusion, these results demonstrated that YPFS could inhibit NLRP3 inflammasome components to attenuate the inflammatory response in asthma.

[Explore pharmacological mechanism of glycyrrhizin based on systems pharmacology].

To explore the pharmacological mechanism of glycyrrhizin with series methods of systems pharmacology, main diseases related to glycyrrhizin were obtained by text mining tool; and the target proteins of glycyrrhizin were obtained via the database of Polysearch and PubChem. Then, the target proteins interaction network of glycyrrhizin was built using the software called Cytoscape. Next, the protein groups related to glycyrrhizin were analyzed by using Gene Ontology (GO) tool, and the action pathway of its target proteins was analyzed by using enrichment method. Text mining results showed that the related diseases of glycyrrhizin included chronic hepatitis C, chronic hepatitis, hepatitis, HIV virus, liver cancer and so on. Gene ontology analysis indicated that glycyrrhizin played a role mainly through modification of proteins and chromatin. The signaling pathway enrichment results showed that the main action proteins of glycyrrhizin were related to MAPK signaling pathway, toll-like receptor signaling pathway, neurotrophic factor signaling pathway, cancer and apoptosis pathways. So we can conclude that glycyrrhizin may exert its biological functions primarily by regulating multiple pathways such as MAPK signaling pathway and Toll-like receptors signaling pathway. The pharmacological action of a drug can be rapidly and comprehensively analyzed by the ways of systems pharmacology.

Syntheses and crystal structures of tetracopper(II) complexes bridged by asymmetric N,N'-bis(substituted)oxamides: Molecular docking, DNA-binding and in vitro anticancer activity.

Two new tetranuclear copper(II) complexes of the formulae [Cu4(oxbm)2(phen)2](NO3)2⋅6H2O (1) and [Cu4(oxbpa)2(phen)2](ClO4)2·4H2O (2), where H3oxbm and H3oxbpa stand for N-(2-aminopropyl)-N'- (2-carboxylatophenyl)oxamide and N-hydroxypropyl-N'-(2-carboxylatophenyl)oxamide, respectively, and phen is 1,10-phenanthroline, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR and electronic spectrum studies, and X-ray single crystal diffraction. In the two tetracopper(II) complexes, the presence of the circular tetracopper(II) cations is assembled by a pair of cis-oxamido-bridged dicopper(II) units through carboxyl bridges, in which Cu1 is located in a distorted square-planar environment, while Cu2 is in a distorted square-pyramidal geometry. Numerous hydrogen bonds link complex 1 or 2 into a 2-D infinite network. The interactions of the two tetracopper(II) complexes with DNA are investigated both theoretically and experimentally, revealing that these tetracopper(II) complexes can interact with HS-DNA in the mode of intercalation, and complex 1 possesses stronger intercalating ability. The molecular docking of the two tetranuclear copper(II) complexes with the self-complementary DNA duplex of sequence d(ACCGACGTCGGT)2 facilitates the binding events. Cytotoxicity experiments indicate that the two tetracopper(II) complexes exhibit cytotoxic effects against human hepatocellular carcinoma cell SMMC-7721 and human lung adenocarcinoma cell A549. Interestingly, the cytotoxic activities of the two tetracopper(II) complexes are consistent with their DNA-binding abilities, following the order of 1>2. The main results suggest that different bridging ligands in tetracopper(II) complexes may play an important role in the DNA-binding properties and cytotoxic activities.