RESUMO
Polo-like kinase 1 (PLK1) is an attractive therapeutic target for the treatment of tumors, as it is an essential cell-cycle regulator frequently overexpressed in tumor tissues. PLK1 can promote tumor invasion and metastasis, and is often associated with poor prognosis in cancer patients. However, no PLK1 inhibitor has been granted marketing approval until now. Therefore, more potentially promising PLK1 inhibitors need to be investigated. In this study, a series of novel inhibitors targeting PLK1 was designed and optimized derived from a new scaffold. After synthesis and characterization, we obtained the structure-activity relationship and led to the discovery of the most promising compound 30e for PLK1. The antiproliferative activity against HCT116 cells (IC50 = 5 nM versus 45 nM for onvansertib) and the cellular permeability and efflux ratio were significantly improved (PappAâB = 2.03 versus 0.345 and efflux ratio = 1.65 versus 94.7 for 30e and onvansertib, respectively). Further in vivo studies indicated that 30e had favorable antitumor activity with 116.2% tumor growth inhibition (TGI) in comparison with TGI of 43.0% for onvansertib. Furthermore, 30e improved volume of tumor tissue distribution in mice as compared to onvansertib. This initial study on 30e holds promise for further development of an antitumor agent.
Assuntos
Neoplasias , Inibidores de Proteínas Quinases , Animais , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases , Linhagem Celular Tumoral , Proliferação de Células , Quinase 1 Polo-LikeRESUMO
The co-crystal structure of Compound 6b with tubulin was prepared and solved for indicating the binding mode and for further optimization. Based on the co-crystal structures of tubulin with plinabulin and Compound 6b, a total of 27 novel A/B/C-rings plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human lung cancer NCI-H460 cell line. The optimum phenoxy-diketopiperazine-type Compound 6o exhibited high potent cytotoxicity (IC50â¯=â¯4.0â¯nM) through SAR study of three series of derivatives, which was more potent than plinabulin (IC50â¯=â¯26.2â¯nM) and similar to Compound 6b (IC50â¯=â¯3.8â¯nM) against human lung cancer NCI-H460 cell line. Subsequently, the Compound 6o was evaluated against other four human cancer cell lines. Both tubulin polymerization assay and immunofluorescence assay showed that Compound 6o could inhibit microtubule polymerization efficiently. Furthermore, theoretical calculation of the physical properties and molecular docking were elucidated for these plinabulin derivatives. The binding mode of Compound 6o was similar to Compound 6b based on the result of molecular docking. The theoretical calculated LogPo/w and PCaco of Compound 6o were better than Compound 6b, which could enhance its cytostatic activity. Therefore, Compound 6o might be developed as a novel potent anti-microtubule agent.
Assuntos
Antineoplásicos/farmacologia , Dicetopiperazinas/farmacologia , Desenvolvimento de Medicamentos , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Dicetopiperazinas/síntese química , Dicetopiperazinas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
To determine if job stress, health, and presenteeism differ between healthcare workers at Chinese public and private hospitals. This cross-sectional study analyzed the records of 1080 healthcare workers in eastern, central, and western China for the period from January2015 through November2015. Data on challenge stress, hindrance stress, health, and presenteeism were collected. Using univariate and multivariate regression and SPSS, we investigated differences between Chinese public and private hospitals in China. Challenge stress, hindrance stress, and presenteeism, but not health status, significantly differed between healthcare workers at public and private hospitals in China. Challenge stress and hindrance stress were significantly higher in public hospitals, while presenteeism was significantly lower in private hospitals. The significant differences between public and private hospitals are attributable to differences in the business practices and management of public and private hospitals. To achieve successful long-term medical reform in China, the adverse effects of psychosocial factors should be considered in future research plans and policies. Chinese hospitals urgently require improvements in management and leadership. Reform efforts should encompass fields such as management science, psychology, and the behavioral sciences.
Assuntos
Pessoal de Saúde/estatística & dados numéricos , Nível de Saúde , Hospitais Privados , Hospitais Públicos , Estresse Ocupacional/epidemiologia , Presenteísmo/estatística & dados numéricos , Pessoal Administrativo , Adulto , Pessoal Técnico de Saúde , China/epidemiologia , Estudos Transversais , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Estresse Ocupacional/psicologia , Farmacêuticos , Médicos , Adulto JovemRESUMO
MBRI-001, a deuterium-substituted plinabulin derivative, has been reported to have better pharmacokinetic and similar antitumor effects in comparison with plinabulin. In this approach, we further carried out its polymorphs, co-crystal structure of MBRI-001-tubulin and tubulin inhibition study. Among the different polymorphs, Form F (MBRI-001/H2O) was prepared and evaluated, which had better physical stability and suitable process for scale-up production. Co-crystal structure of MBRI-001-tubulin (PDB:5XI5) was prepared and analyzed. The result of tubulin polymerization assay demonstrated that MBRI-001 could inhibit tubulin polymerization which was similar as plinabulin. Subsequently, the anti-proliferative activities of plinabulin and MBRI-001 were evaluated against two different human lung cancer cell lines. In vivo study, MBRI-001 revealed similar antitumor inhibition in comparison with plinabulin in A549 xenograft tumor model. Therefore, we suggested that MBRI-001 could be developed as a promising anti-cancer agent in near future.
Assuntos
Dicetopiperazinas/química , Moduladores de Tubulina/química , Tubulina (Proteína)/química , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Deutério/química , Dicetopiperazinas/metabolismo , Dicetopiperazinas/farmacologia , Dicetopiperazinas/uso terapêutico , Humanos , Camundongos , Camundongos Nus , Conformação Molecular , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Estrutura Terciária de Proteína , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêuticoRESUMO
We have developed an efficient protocol for the synthesis of C-glycosylated phenanthridines. Tetrafuranos-4-yl and pentapyranos-5-yl radicals, generated from K2S2O8-mediated oxidative decarboxylation of furan- and pyranuronic acids, undergo attack to 2-isocyanodiphenyls and ensuing homolytic aromatic substitution to provide diverse C-glycosylated phenanthridines in satisfactory yields without resort to transition metals. This reaction tolerates various functional groups, and enables ready synthesis of complex oligosaccharide-based phenanthridines. The C-glycosylated phenanthridine derived from ß-cyclodextrin has been prepared, which might be potential in medicinal and biological chemistry due to its flexible conformation.
RESUMO
MBRI-001 was demonstrated preliminary better pharmacokinetics and antitumor effects than that of plinabulin in vivo. In this approach, we further carried out systematic pharmacokinetic and pharmacodynamic study of MBRI-001 in vitro and in vivo. MBRI-001 was tested stable in rat plasma and more stable in liver microsomes than plinabulin in vitro. In vivo, MBRI-001 could be distributed rapidly and widely in various tissues, especially the concentration of MBRI-001 in lung was remarkably higher than other tissues. Excretion study indicated that MBRI-001 might been decomposed and excreted as metabolites. Additionally, the combination treatment of MBRI-001 and gefitinib revealed better antitumor inhibition rate than monotherapy in vivo. Therefore, we suggest that MBRI-001 could be developed as a promising anti-cancer agent in near future.
Assuntos
Antineoplásicos/química , Dicetopiperazinas/química , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Deutério/química , Dicetopiperazinas/metabolismo , Dicetopiperazinas/farmacocinética , Dicetopiperazinas/uso terapêutico , Feminino , Meia-Vida , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ligação Proteica , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a derivative of plinabulin), a total of 18 novel plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e exhibited potent activities with IC50 at 1.56 and 1.72â¯nM, respectively. The tubulin polymerization assay indicated that these derivatives could inhibit microtubule polymerization. Furthermore, the interaction between tubulin and these compounds were elucidated by molecular docking. The binding modes of Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H-π interaction was observed between the aromatic hydrogen of thiophene moiety with Phe20, which could enhance their binding affinities.
Assuntos
Antineoplásicos/síntese química , Dicetopiperazinas/química , Desenho de Fármacos , Moduladores de Tubulina/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Dicetopiperazinas/metabolismo , Dicetopiperazinas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Neoplasias Pancreáticas/patologia , Estrutura Terciária de Proteína , Solubilidade , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologiaRESUMO
Deuterium-enriched and fluorine-substituted compounds have been widely applied in drug discovery due to their advantages in the studies of clinical pharmacokinetics and metabolic profiles. Herein we synthesized a library of deuterated and fluorine-substituted plinabulin derivatives, and all 15 D- or F-compounds were characterized by MS, [Formula: see text] NMR and [Formula: see text]. Their antitumor activities were evaluated against human Jurkat T lymphocyte cells.
Assuntos
Antineoplásicos/síntese química , Deutério/química , Dicetopiperazinas/síntese química , Flúor/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Humanos , Células Jurkat , Espectrometria de Massas , Estrutura Molecular , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Zuranolone (SAGE-217) is a neuroactive steroid (γ-aminobutyric acid)A (GABAA) receptor positive allosteric modulator (PAM) as the first oral drug approved by the FDA in 2023, which is used to treat patients with postpartum depression (PPD). SAGE-217 has a "black box" warning with impairing ability to drive or engage in other potentially hazardous activities. In addition, SAGE-217 can cause CNS depressant effects such as somnolence and confusion, suicidal thoughts and behavior and embryo-fetal toxicity. Based on the structure-activity relationship (SAR) of SAGE-217, a total of 28 neuroactive steroids with novel pharmacophore at C-21 modulated SAGE-217 derivatives were designed and synthesized. The biological activities were evaluated by both synaptic α1ß2γ2 GABAA receptor and extrasynaptic α4ß3δ GABAA receptor cell assays. The optimal compound S28 exhibited much more potent potency and similar efficacy at extrasynaptic GABAA receptor than SAGE-217. Different from above, compound S28 exhibited similar potency and lower efficacy at synaptic GABAA receptor than SAGE-217, which were consistent with the analysis of molecular docking and dynamics simulation results. The appropriate lower efficacy at synaptic GABAA receptor of compound S28 might contribute to reduce the side effects of excessive sedation. Furthermore, compound S28 was demonstrated to have excellent in vivo pharmacokinetic (PK) parameters, robust in vivo pharmacodynamic (PD) effects and good safety profiles. Therefore, compound S28 represents a potentially promising treatment of PPD candidate that warrants further investigation.
Assuntos
Receptores de GABA-A , Receptores de GABA-A/metabolismo , Relação Estrutura-Atividade , Humanos , Animais , Estrutura Molecular , Relação Dose-Resposta a Droga , Camundongos , Neuroesteroides/farmacologia , Neuroesteroides/metabolismo , Neuroesteroides/síntese química , Neuroesteroides/química , Simulação de Acoplamento Molecular , Regulação Alostérica/efeitos dos fármacos , Masculino , Moduladores GABAérgicos/farmacologia , Moduladores GABAérgicos/síntese química , Moduladores GABAérgicos/química , Farmacóforo , Pregnanolona , PirazóisRESUMO
Breast cancer is one of the most common malignant tumors in women worldwide, with the majority of cases showing expression of estrogen receptors (ERs). Although drugs targeting ER have significantly improved survival rates in ER-positive patients, drug resistance remains an unmet clinical need. Fulvestrant, which overcomes selective estrogen receptor modulator (SERM) and AI (aromatase inhibitor) resistance, is currently the only long-acting selective estrogen receptor degrader (SERD) approved for both first and second-line settings. However, it fails to achieve satisfactory efficacy due to its poor solubility. Therefore, we designed and synthesized a series of novel scaffold (THC) derivatives, identifying their activities as ER antagonists and degraders. G-5b, the optimal compound, exhibited binding, antagonistic, degradation or anti-proliferative activities comparable to fulvestrant in ER+ wild type and mutants breast cancer cells. Notably, G-5b showed considerably improved stability and solubility. Research into the underlying mechanism indicated that G-5b engaged the proteasome pathway to degrade ER, subsequently inhibiting the ER signaling pathway and leading to the induction of apoptosis and cell cycle arrest events. Furthermore, G-5b displayed superior in vivo pharmacokinetics and pharmacodynamics properties, coupled with a favorable safety profile in the MCF-7 tamoxifen-resistant (MCF-7/TR) tumor xenograft model. Collectively, G-5b has emerged as a highly promising lead compound, offering potent antagonistic and degradation activities, positioning it as a novel long-acting SERD worthy of further refinement and optimization.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Antagonistas do Receptor de Estrogênio , Fulvestranto , Antagonistas de Estrogênios/farmacologia , Tamoxifeno/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Receptor alfa de Estrogênio/metabolismoRESUMO
The neurokinin-3 receptor (NK3R) is one of three receptors that recognize neurokinins. The finding that pharmacological blockade of neurokinin B (NKB) signaling with an oral NK3R antagonist can significantly improve hot flash symptoms independent of any hormonal effect fits strongly suggest that NK3R is a viable drug target and that drugs targeting this receptor could be novel pharmacotherapies. Currently no NK3R ligands have been approved for the treatment of human disorders. Herein, we designed and synthesized a series of novel imidazolepiperazine derivatives (16a-16x, 20a-20f, 29a-29m) and performed molecular docking to confirm the design, among which the target compound 16x exhibited promising inhibitory activity against NK3R (IC50 = 430.60 nM) with excellent membrane permeability (Papp, A-B = 37.6 × 10-6 cm/s, ER < 1) and oral bioavailability (F% = 93.6%). Our in vivo studies demonstrated that 16x was orally active, efficacious, and well-tolerated in ovariectomy (OVX) model to suppress blood luteinizing hormone levels, which suggests that 16x is a viable lead compound for further optimization and development.
Assuntos
Neurocinina B , Receptores da Neurocinina-3 , Feminino , Humanos , Simulação de Acoplamento Molecular , Transdução de Sinais , OvariectomiaRESUMO
Triple negative breast cancer (TNBC) is a subtype of breast cancer with significant malignancy and poor prognosis but effective treatments are limited. Given the critical role of CDK4/6 in cell cycle and the apparent success of CDK4/6 inhibitors against certain cancer, this study attempted to utilize hydrophobic tagging technology to develop a CDK4/6 degrader against TNBC. We based on the chemical structure of the major metabolite of a clinically approved CDK4/6 inhibitor, abemaciclib, to synthesize three compounds and evaluated their in vitro cytotoxicity. LPM3770277 stood out as the most promising compound which was further confirmed by a series of binding and CDK4/6 degradation studies. LPM3770277 was able to bind to CDK4/6, and time-dependently and dose-dependently increased CDK4/6 protein degradation. Mechanistic study revealed that LPM3770277 exerted its CDK4/6 degradation effect via two machineries: proteasome and lysosome-promoted autophagy. Using in vivo TNBC xenograft cancer model, we found that LPM3770277 demonstrated superior anti-tumor efficacy and safety as compared to abemaciclib, although both compounds exerted similar effects on cell cycle arrest. In conclusion, this study for the first time developed and characterized a CDK4/6 degrader against TNBC using hydrophobic tags, which strongly suggests the viability of hydrophobic tags as a strategy to develop potential treatments against TNBC.
RESUMO
The gonadotropin releasing hormone receptor (GnRH-R) is a G protein-coupled receptor (GPCR) belonging to the rhodopsin family. GnRH-R antagonists suppress testosterone to castrate level more rapidly than gonadotropin releasing hormone agonists but lack the flare phenomenon often seen during the early period of GnRH-R agonist treatment. Recently orgovyx (relugolix) was approved as the first oral GnRH-R antagonist for the treatment of advanced prostate cancer. However, orgovyx has demonstrated poor pharmacokinetic profile with low oral bioavailability and high efflux. Here, we rationally designed and synthesized a series of derivatives (13a-m, 21a-i) through the modification and structure-activity relationship study of relugolix, which led to the discovery of 21a as a highly potent GnRH-R antagonist (IC50 = 2.18 nM) with improved membrane permeability (Papp, A-B = 0.98 × 10-6 cm/s) and oral bioavailability (F % = 44.7). Compound 21a showed high binding affinity (IC50 = 0.57 nM) and potent in vitro antagonistic activity (IC50 = 2.18 nM) at GnRH-R. 21a was well tolerated and efficacious in preclinical studies to suppress blood testosterone levels, which merits further investigation as a candidate novel GnRH-R antagonist for clinical studies.
Assuntos
Receptores LHRH , Rodopsina , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Compostos de Fenilureia , Pirimidinas , Pirimidinonas , Receptores LHRH/metabolismo , TestosteronaRESUMO
Pimavanserin is a selective 5-HT2A receptor antagonist and inverse agonist approved by the FDA in 2016, which is used to treat patients with Parkinson's disease psychosis (PDP). But pimavanserin has potential risk with increasing mortality in elderly patients and also increasing the risk of QT interval prolongation in patients. Therefore, searching for new drugs with high efficacy and low toxicity is urgently needed. Based on the docking study of pimavanserin, a series of novel pimavanserin derivatives (7-1â¼7-37) were designed and synthesized. The biological activities were evaluated by cell assays and compound 7-16 exhibited 50-fold higher 5-HT2A receptor antagonist activity (IC50 = 0.54 vs 27.3 nM) and 23-fold higher inverse agonist activity (IC50 = 2.1 vs 50 nM) than pimavanserin. Moreover, 7-16 showed increased potency window between the 5-HT2A and hERG activities than pimavanserin. Furthermore, compound 7-16 demonstrated excellent in vitro and in vivo pharmacokinetics, 4-fold more improvement in functional activity in vivo, and good safety profile. Therefore, compound 7-16 represents a potentially promising candidate as a novel anti-PDP agent that warrants further investigation.
Assuntos
Antipsicóticos , Doença de Parkinson , Transtornos Psicóticos , Idoso , Antipsicóticos/uso terapêutico , Humanos , Doença de Parkinson/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Receptor 5-HT2A de Serotonina , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , UreiaRESUMO
Myricetin is a natural dietary flavonoid compound with multiple activities, such as anti-oxidant, anti-inflammatory, anti-carcinogenic and anti-proliferative effects. However, myricetin exhibited substantial limitations, such as poor water-solubility, and low stability in body when it was administrated by oral. To solve these problems, we designed and synthesized a series of derivatives based on the structure of myricetin. M10 was produced by adding a hydrophilic glycosylation group and then forming a sodium salt derivative, which exhibited excellent water-solubility (>100â¯mg/mL), and better stability in Wistar rat plasma and liver microsomes. In vivo study, M10 exhibited higher efficacy than myricetin and mesalazine in a dextran sulfate sodium (DSS) induced mice model with ulcerative colitis. In addition, M10 also exhibited high safety (LD50â¯>â¯5â¯g/kg) in mice. Based on these results, M10 could be developed as a potential therapeutic agent for treatment of ulcerative colitis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Flavonoides/uso terapêutico , Lactose/análogos & derivados , Lactose/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Colite Ulcerativa/induzido quimicamente , Colo/patologia , Sulfato de Dextrana , Estabilidade de Medicamentos , Feminino , Flavonoides/síntese química , Flavonoides/química , Flavonoides/farmacocinética , Glicosilação , Meia-Vida , Lactose/síntese química , Lactose/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/metabolismo , Ratos Wistar , SolubilidadeRESUMO
BACKGROUND: We examined the effects of challenge stress and hindrance stress on general health and presenteeism among Chinese healthcare workers. METHODS: Structural equation modeling was used to evaluate data from a national hospital survey in China (n = 1392). Job stress, general health, and presenteeism were measured by the Perceived Ability to Work Scale, the 8-item Short-Form Health Survey, and the Challenge- and Hindrance-Related Self-reported Stress Scale. RESULTS: Challenge stress and hindrance stress were significantly positively correlated (ß = 0.62, SE = 0.021; p < 0.001). Challenge stress was directly negatively associated with presenteeism (ß = -0.05, SE = 0.037; p < 0.001), while hindrance stress was positively associated with presenteeism (ß = 0.25, SE = 0.040; p < 0.001). These associations with presenteeism were partially mediated by health. CONCLUSIONS: Hospital managers should provide healthcare workers with an appropriate level of challenge, but employee health is the most important consideration. Further efforts targeting job stress and health of junior healthcare workers are required.
Assuntos
Pessoal de Saúde/psicologia , Nível de Saúde , Estresse Ocupacional/psicologia , Presenteísmo/estatística & dados numéricos , Adulto , China , Feminino , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , Cultura Organizacional , Fatores Socioeconômicos , Carga de Trabalho/psicologia , Adulto JovemRESUMO
BACKGROUND: Presenteeism affects the performance of healthcare workers. This study examined associations between job stress, affective commitment, and presenteeism among healthcare workers. METHODS: To investigate the relationship between job stress, affective commitment, and presenteeism, structural equation modeling was used to analyze a sample of 1392 healthcare workers from 11 Class A tertiary hospitals in eastern, central, and western China. The mediating effect of affective commitment on the association between job stress and presenteeism was examined with the Sobel test. RESULTS: Job stress was high and the level of presenteeism was moderate among healthcare workers. Challenge stress and hindrance stress were strongly correlated (ß = 0.62; p < 0.05). Affective commitment was significantly and directly inversely correlated with presenteeism (ß = -0.27; p < 0.001). Challenge stress was significantly positively correlated with affective commitment (ß = 0.15; p < 0.001) but not with presenteeism. Hindrance stress was significantly inversely correlated with affective commitment (ß = -0.40; p < 0.001) but was significantly positively correlated with presenteeism (ß = 0.26; p < 0.001). CONCLUSIONS: This study provides important empirical data on presenteeism among healthcare workers. Presenteeism can be addressed by increasing affective commitment and challenge stress and by limiting hindrance stress among healthcare workers in China.