Design, synthesis and antifungal activity of threoninamide carbamate derivatives via pharmacophore model.

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

Design, synthesis, and fungicidal activities of novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties.

BACKGROUND: To study the effect of changing the piperidine ring of oxathiapiprolin on the fungicidal activity, we designed and synthesized novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties, and studied their fungicidal activities against Phytophthora capsici in vitro. RESULTS: These derivatives showed moderate to good fungicidal activities against Phytophthora capsici, two oxime ether derivatives showed higher fungicidal activity in vitro than dimethomorph (EC50  = 0.1331 µg mL-1 ) and comparable to oxathiapiprolin (EC50  = 0.0042 µg mL-1 ). Oxime ester derivatives showed significantly reduced activities compared with oxime ether derivatives. Most of these derivatives showed broad-spectrum fungicidal activity against the other eight kinds of fungi. Moreover, four derivatives exhibited good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. The hyphae morphology study showed that compound 10d might cause mycelial abnormalities of Phytophthora capsici. CONCLUSION: The activity of 10b against Phytophthora infestans was better than that of mandipropamid, and compound 10d exhibited higher fungicidal activities against Pseudoperonospora cubensis and Phytophthora infestans than mandipropamid. These two derivatives emerged as promising candidates for antifungal drugs. © 2023 Society of Chemical Industry.

Corrigendum: The association between cognitive deficits and clinical characteristic in first-episode drug naïve patients with schizophrenia.

[This corrects the article DOI: 10.3389/fpsyt.2021.638773.].

Corrigendum: The association between metabolic disturbance and cognitive impairments in early-stage schizophrenia.

[This corrects the article DOI: 10.3389/fnhum.2020.599720.].

Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 µg/mL) which is higher than dimethomorph (EC50 = 0.1148 µg/mL) and diacetylenyl amide (EC50 = 0.040 µg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

The Association Between Cognitive Deficits and Clinical Characteristic in First-Episode Drug Naïve Patients With Schizophrenia.

Background: Schizophrenia is a severe mental disease which characterized by positive symptom, negative symptom, general pathology syndrome and cognitive deficits. In recent years, many studies have investigated the relationship between cognitive deficits and clinical characteristics in schizophrenia, but relatively few studies have been performed on first-episode drug-naïve patients. Methods: Eighty seven first-episode drug-naïve schizophrenia patients were assessed for positive symptom, negative symptom, general pathology symptom and cognitive deficits from the Positive and Negative Symptom Scale and MATRICS Consensus Cognitive Battery. Psychotics depression were assessed using the Calgary depressing scale for schizophrenia. The relationship between clinical characteristics and cognitive deficits were assessed using correlation analysis and linear regression analysis. Results: The prevalence of cognitive deficits among the patients in our study was 85.1% (74/87) which was much higher than that in the general population. According to correlation analysis, negative symptom was negatively correlated with speed of processing and social cognition, and general pathology showed a negative correlation with attention/vigilance. In addition, a positive correlation was found between age and speed of processing. No correlation was found between cognitive deficits and positive symptom. Conclusions: This study confirmed that negative symptom is negatively related with some domains of cognitive function in first-episode drug naïve schizophrenia patients. Trail Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

Corrigendum: The Association Between Cognitive Deficits and Clinical Characteristic in First-Episode Drug Naïve Patients With Schizophrenia.

[This corrects the article DOI: 10.3389/fpsyt.2021.638773.].

The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia.

Background: Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia. Methods: In this study, we recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment. Results: Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p < 0.05), while such association was not found in further multiple regression analysis. Conclusions: Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia. Trial Registration: Clinicaltrials.gov, NCT03451734. Registered March 2, 2018 (retrospectively registered).

Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients

Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

Corrigendum: Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients.

[This corrects the article DOI: 10.3389/fphar.2020.00739.].