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1.
Pulm Ther ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833146

ABSTRACT

INTRODUCTION: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. METHODS: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. RESULTS: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. CONCLUSIONS: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

2.
Discov Med ; 36(183): 690-698, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38665018

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients with sleep disorders may be at greater risk for respiratory exacerbation or death compared to those without. After being infected with COVID-19, patients have many symptoms related to sleep disorders, especially those with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. This study aimed to evaluate sleep disturbances in patients with severe SARS-CoV-2 infection who were treated in the Intensive Care Unit (ICU). METHODS: This cross-sectional study used the questionnaire provided by the Vietnam Sleep Disorder Study (ViSDiS) research, elaborated by the Vietnam Society of Sleep Medicine (VSSM). Seventy-seven COVID-19 patients were included. RESULTS: There was a significant difference in sleep status before and after SARS-CoV-2 infection among participants. Up to 83% of them reported experiencing insomnia after illness, 60% reported having frequent nightmares, and more than half of participants reported nocturia (p < 0.0001). More than 81.8% of patients with severe SARS-CoV-2 infection were unsatisfied with their sleep quality during hospitalization After SARS-CoV-2 infection, only 2.6% of participants felt they had good quality sleep (p < 0.0001). The majority of patients suffered from fatigue after SARS-CoV-2 infection, including a lack of energy, feeling heaviness in their limbs, aggravation of pre-existing sleep disorders, idleness, constant fatigue throughout the day, and difficulty concentrating. CONCLUSION: Sleep problems are highly prevalence among hospitalized patients with severe COVID-19 in the ICU. Healthcare providers should pay attention to sleep problems and their associated symptoms to initiate appropriate treatment to improve severe COVID-19 patients' health status and minimize the risk of death.


Subject(s)
COVID-19 , Intensive Care Units , SARS-CoV-2 , Sleep Wake Disorders , Humans , COVID-19/epidemiology , COVID-19/complications , COVID-19/therapy , Male , Female , Intensive Care Units/statistics & numerical data , Middle Aged , Vietnam/epidemiology , Cross-Sectional Studies , Sleep Wake Disorders/epidemiology , Aged , Adult , Surveys and Questionnaires , Sleep Quality , Severity of Illness Index
3.
Anticancer Agents Med Chem ; 24(1): 18-29, 2024.
Article in English | MEDLINE | ID: mdl-37957868

ABSTRACT

Since coumarin and hydroxamic acid compounds are well-known in medicinal chemistry, a variety of their derivatives have been highlighted due to their potential uses for plentiful treatments. Different compounds of their derivatives acting through diverse activities, such as anti-tumor, anti-cancer, anti-inflammation, and histone deacetylase inhibition, have been comprehensively investigated by many researchers over the years. This present review provides the latest literature and knowledge on hydroxamic acids derived from coumarin. Overall, some recent advancements in biological activities of hybrid derivatives of hydroxamic acids containing coumarin moieties in medicinal chemistry are discussed.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Hydroxamic Acids/pharmacology , Hydroxamic Acids/chemistry , Neoplasms/drug therapy , Coumarins/pharmacology , Coumarins/chemistry , Histone Deacetylases/metabolism , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
4.
Ophthalmologie ; 120(11): 1098-1106, 2023 Nov.
Article in German | MEDLINE | ID: mdl-37874364

ABSTRACT

BACKGROUND: Glaucoma is a widespread ophthalmological disease. Knowledge about the spread of the disease in the population is necessary with respect to further questions on comorbidities, risk factors and the provision of care. OBJECTIVE: An analysis of the use of glaucoma medications and the prevalence of glaucoma in an urban adult population was carried out. MATERIAL AND METHODS: The Hamburg City Health Study (HCHS) is a prospective, long-term, population-based cohort study that includes a random sample of 45,000 participants aged between 45 and 79 years from the general population of Hamburg, Germany. Apart from various medical parameters, data include premedication and the medical history of the participants. The use of antiglaucomatous medication among the first 10,000 study participants was analyzed and the prevalence of glaucoma was estimated according to the use of medications as well as by the self-reported history of glaucoma. Descriptive analysis and logistic regression analysis were performed to analyze the data and to calculate correlations by age and gender. RESULTS: In the study population 319 persons were on medication to lower the intraocular pressure (IOP, mean age 67.1 years, SD = 7.57 years), which is equivalent to an estimated prevalence of 3.35% (95% confidence interval, CI 3.00-3.70%). A positive correlation was observed between age and the use of IOP-lowering medication, which is statistically highly significant (p = < 0.001). The analysis by gender showed a slightly higher prevalence among women, which was not statistically significant. The estimated prevalence according to glaucoma medication and history were only partly congruent. DISCUSSION: This estimated prevalence of glaucoma is comparable to other epidemiological studies. The study results cover not only patients with manifest glaucoma but also persons who were treated for ocular hypertension. The inconsistency between the prevalence of glaucoma medication and the diagnosis of glaucoma can be explained by different treatment strategies and also by information deficits.


Subject(s)
Glaucoma , Humans , Adult , Female , Middle Aged , Aged , Prevalence , Cohort Studies , Prospective Studies , Glaucoma/drug therapy , Intraocular Pressure
5.
Nat Prod Res ; : 1-8, 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37859419

ABSTRACT

Eight new caffeyl hydrazide derivatives (4a-4h) were synthesised via a convenient esterification of caffeic acid with some substituted aryl acid hydrazides. The synthesised caffeyl derivatives were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. The fluorobenzoylhydrazide derivatives 4f, 4 g and 4h were found to be the most powerful anti-inflammatory compounds with IC50 values ranging from 11.90 to 24.17 µM, which were more potent than the reference compound L-NMMA (IC50 32.8 µM). Additionally, synthesised compounds have been rationalised by using molecular docking studies which were performed in order to understand insights on the action mechanism of newly synthesised inhibitors against inflammatory mediator (iNOS). Obtained data indicate that compounds 4f, 4h, 4a and 4 g were observed to effectively bind to iNOS receptor with dock score values of -11.62, -10.81, -10.78 and -10.51 kcal/mol, respectively.

6.
Sci Rep ; 13(1): 17515, 2023 10 16.
Article in English | MEDLINE | ID: mdl-37845236

ABSTRACT

Difficulty falling asleep is one of the typical insomnia symptoms. However, intervention therapies available nowadays, ranging from pharmaceutical to hi-tech tailored solutions, remain ineffective due to their lack of precise real-time sleep tracking, in-time feedback on the therapies, and an ability to keep people asleep during the night. This paper aims to enhance the efficacy of such an intervention by proposing a novel sleep aid system that can sense multiple physiological signals continuously and simultaneously control auditory stimulation to evoke appropriate brain responses for fast sleep promotion. The system, a lightweight, comfortable, and user-friendly headband, employs a comprehensive set of algorithms and dedicated own-designed audio stimuli. Compared to the gold-standard device in 883 sleep studies on 377 subjects, the proposed system achieves (1) a strong correlation (0.89 ± 0.03) between the physiological signals acquired by ours and those from the gold-standard PSG, (2) an 87.8% agreement on automatic sleep scoring with the consensus scored by sleep technicians, and (3) a successful non-pharmacological real-time stimulation to shorten the duration of sleep falling by 24.1 min. Conclusively, our solution exceeds existing ones in promoting fast falling asleep, tracking sleep state accurately, and achieving high social acceptance through a reliable large-scale evaluation.


Subject(s)
Sleep Initiation and Maintenance Disorders , Wearable Electronic Devices , Humans , Acoustic Stimulation , Sleep/physiology , Polysomnography
7.
Front Neurol ; 14: 1124059, 2023.
Article in English | MEDLINE | ID: mdl-37305754

ABSTRACT

Purpose: In this study, we described "PT for Sleep Apnea", a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA). Methods: The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training. Results: The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea. Conclusion: In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.

8.
J Pers Med ; 13(5)2023 May 10.
Article in English | MEDLINE | ID: mdl-37240979

ABSTRACT

Symptoms control remains challenging for most patients with asthma. This study was conducted to evaluate the level of asthma symptoms control and lung function over 5 years of GINA (Global INitiative for Asthma) implementation. We included all patients with asthma who had been managed following GINA recommendations at the Asthma and COPD Outpatient Care Unit (ACOCU) of the University Medical Center in Ho Chi Minh City, Vietnam from October 2006 to October 2016. Of 1388 patients with asthma managed following GINA recommendations, the proportion of patients with well-controlled asthma significantly improved from 2.6% at baseline to 66.8% at month 3, 64.8% at year 1, 59.6% at year 2, 58.6% at year 3, 57.7% at year 4, and 59.5% at year 5 (p < 0.0001 for all comparisons). The proportion of patients with persistent airflow limitation significantly decreased from 26.7% at baseline to 12.6% at year 1 (p < 0.0001), 14.4% at year 2 (p < 0.0001), 15.9% at year 3 (p = 0.0006), 12.7% at year 4 (p = 0.0047), and 12.2% at year 5 (p = 0.0011). In patients with asthma managed according to GINA recommendations, asthma symptoms control and lung function improved after 3 months and the improvement was sustained over 5 years.

9.
Pulm Ther ; 9(3): 295-307, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37209374

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) usually suffer from post-acute sequelae of coronavirus disease 2019 (PASC). Pulmonary fibrosis (PF) has the most significant long-term impact on patients' respiratory health, called post-COVID-19 pulmonary fibrosis (PC19-PF). PC19- PF can be caused by acute respiratory distress syndrome (ARDS) or pneumonia due to COVID-19. The risk factors of PC19-PF, such as older age, chronic comorbidities, the use of mechanical ventilation during the acute phase, and female sex, should be considered. Individuals with COVID-19 pneumonia symptoms lasting at least 12 weeks following diagnosis, including cough, dyspnea, exertional dyspnea, and poor saturation, accounted for nearly all disease occurrences. PC19-PF is characterized by persistent fibrotic tomographic sequelae associated with functional impairment throughout follow-up. Thus, clinical examination, radiology, pulmonary function tests, and pathological findings should be done to diagnose PC19-PF patients. PFT indicated persistent limitations in diffusion capacity and restrictive physiology, despite the absence of previous testing and inconsistency in the timeliness of assessments following acute illness. It has been hypothesized that PC19-PF patients may benefit from idiopathic pulmonary fibrosis treatment to prevent continued infection-related disorders, enhance the healing phase, and manage fibroproliferative processes. Immunomodulatory agents might reduce inflammation and the length of mechanical ventilation during the acute phase of COVID-19 infection, and the risk of the PC19-PF stage. Pulmonary rehabilitation, incorporating exercise training, physical education, and behavioral modifications, can improve the physical and psychological conditions of patients with PC19-PF.

10.
Pulm Ther ; 9(2): 271-280, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36991236

ABSTRACT

Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain-Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO2 decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination.

11.
J Pers Med ; 12(12)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36556255

ABSTRACT

Obstructive sleep apnea (OSA) is a common disease that is often under-diagnosed and under-treated in all ages. This is due to differences in morphology, diversity in clinical phenotypes, and differences in diagnosis and treatment of OSA in children and adults, even among individuals of the same age. Therefore, a personalized medicine approach to diagnosis and treatment of OSA is necessary for physicians in clinical practice. In children and adults without serious underlying medical conditions, polysomnography at sleep labs may be an inappropriate and inconvenient testing modality compared to home sleep apnea testing. In addition, the apnea-hypopnea index should not be considered as a single parameter for making treatment decisions. Thus, the treatment of OSA should be personalized and based on individual tolerance to sleep-quality-related parameters measured by the microarousal index, harmful effects of OSA on the cardiovascular system related to severe hypoxia, and patients' comorbidities. The current treatment options for OSA include lifestyle modification, continuous positive airway pressure (CPAP) therapy, oral appliance, surgery, and other alternative treatments. CPAP therapy has been recommended as a cornerstone treatment for moderate-to-severe OSA in adults. However, not all patients can afford or tolerate CPAP therapy. This narrative review seeks to describe the current concepts and relevant approaches towards personalized management of patients with OSA, according to pathophysiology, cluster analysis of clinical characteristics, adequate combined therapy, and the consideration of patients' expectations.

12.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36355556

ABSTRACT

Traditional/herbal medicine has gained increasing interests recently, especially in Asian countries such as Vietnam, due to its diverse therapeutic actions. In the treasure of Vietnamese medicinal plants, one of the potential herbs is the roots of Sophora flavescens Ait. (SF, "Kho sam" in Vietnamese). However, limited information has been reported on the Vietnamese SF compositions and their respective alkaloids' anti-acetylcholinesterase action. Thus, this study investigated the extractions, isolations, identifications, and in-vitro antioxidant, cytotoxicity, and acetylcholinesterase inhibitory activities, of the SF root extracts and their purified alkaloid compounds. To this end, four pure compounds were successfully isolated, purity-tested by HPLC, and structurally identified by spectroscopic techniques of FTIR, MS, and NMR. These compounds, confirmed to be oxysophocarpine, oxymatrine, matrine, and sophoridine, were then determined their therapeutic actions. The SF extracts and the compounds did not possess significant antioxidant activity using the DPPH and MDA assays, and cytotoxicity action using the MTT assay on the MDA-MB-231 breast cancer cell line. On the other hand, the SF total extract yielded a moderate acetylcholinesterase inhibition effect, with an IC50 of 0.1077 ± 0.0023 mg/mL. In summary, the SF extract demonstrated potential effects as an anti-acetylcholinesterase agent and could be further researched to become a pharmaceutical product for diseases related to acetylcholine deficiency, such as dementia.

13.
Front Psychiatry ; 13: 984658, 2022.
Article in English | MEDLINE | ID: mdl-36325524

ABSTRACT

Background: The COVID-19 outbreak witnessed in the autumn of 2021 led to unprecedented changes in healthcare systems in some emerging countries. Many field-hospitals, temporary sites of care for COVID-19 patients, were built around the country and followed by the healthcare workers who were mobilized. This study aimed to measure sleep disorders, depression, and fatigue in volunteers working at field hospitals during the COVID-19 outbreak. Methods: This was a cross-sectional study. The self-report questionnaire was used for each study subject. Sleep characters, including STOP's elements were questioned. Healthcare workers' burnout was detected by using Pichot's questionnaire. Results: One hundred front-line healthcare workers (FHWs), predominantly last year and graduated medical students, were included in the study (86% female subjects). The mean sleep-time of FHWs before, while working, and during the isolation period after working at COVID-19 field hospitals were: 7.78 ± 1.48, 5.71 ± 1.40, and 8.78 ± 2.31 h per day, respectively. Burnout was not a crucial issue for these volunteer subjects. The mean scores of Pichot's Fatigue Scale and Pichot's Depression Scale, measured after 4 weeks working at field hospitals, were 4.18 ± 5.42 and 2.54 ± 3.36, respectively. Thirteen participants were suspected of depression. The fatigue scores decreased significantly in the group who claimed short sleep latency. The factor that increased the depression score was "anxious feeling" (p = 0.001). Other significant factors were "short sleep latency," "observed sleep apnea," "tiredness, daily sleepiness" and "snoring." Conclusion: Appropriate work schedule, better sleep conditions, and mental health support could be helpful for FHWs. The mandatory 2 weeks of isolation after working in field hospitals provided opportunity for FHWs' recovery.

14.
Polymers (Basel) ; 14(22)2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36432951

ABSTRACT

The mini-review deals with borosiloxanes as a class of organoelement compounds that comprise Si-O-B bonds, including individual compounds and polymeric structures. The borosiloxanes first synthesized in the 1950s using simple methods demonstrated very unusual properties but were hydrolytically unstable. However, in recent times, synthetic methods have changed significantly, which made it possible to synthesize borosiloxanes that are resistant to external factors, including atmospheric moisture. Borosiloxanes became important due to their unique properties. For example, borosiloxane liquids acquire a thixotropic behavior due to donor-acceptor interchain interactions. In addition, borosiloxanes are used to produce flame-retardant ceramics. An analysis of the literature sources shows that no review has yet been completed on the topic of borosiloxanes. Therefore, we decided that even a brief outlook of this area would be useful for researchers in this and related fields. Thus, the review shows the evolution of the synthesis methods and covers the studies on the properties of these unique molecules, the latest achievements in this field, and the prospects for their application.

15.
Med Chem ; 17(7): 732-749, 2021.
Article in English | MEDLINE | ID: mdl-32310052

ABSTRACT

BACKGROUND: The target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development. Histone deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing conjugated quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating conjugated 6-hydroxy-2 methylquinazolin- 4(3H)-ones (15a-l) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1. Molecular simulations were finally performed to gain more insight into the structureactivity relationships. RESULTS: It was found that among novel conjugated quinazolinone-based hydroxamic acids synthesized, compounds 15a, 15c and 15f were the most potent, both in terms of HDAC inhibition and cytotoxicity. Especially, compound 15f displayed up to nearly 4-fold more potent than SAHA (vorinostat) in terms of cytotoxicity against MCF-7 cell line with IC50 value of 1.86 µM, and HDAC inhibition with IC50 value of 6.36 µM. Docking experiments on HDAC2 isozyme showed that these compounds bound to HDAC2 with binding affinities ranging from -10.08 to -14.93 kcal/mol compared to SAHA (-15.84 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward SKLu-1than MCF-7 and HepG-2. CONCLUSION: The resesrch results suggest that some hydroxamic acids could emerge for further evaluation and the results are well served as basics for further design of more potent HDAC inhibitors and antitumor agents.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Drug Design , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/pharmacology , Quinazolinones/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chemistry Techniques, Synthetic , Humans , Hydroxamic Acids/chemistry
16.
Bioorg Chem ; 101: 103988, 2020 08.
Article in English | MEDLINE | ID: mdl-32534346

ABSTRACT

Several novel series of hydroxamic acids bearing 2-benzamidooxazole/thiazole (5a-g, 6a-g) or 2-phenylsulfonamidothiazole (8a-c) were designed and synthesized. The compounds were obtained straightforwards via a two step pathway, starting from commercially available ethyl 2-aminooxazole-4-carboxylate or ethyl 2-aminothiazole-4-carboxylate. Biological evaluation showed that these hydroxamic acids generally exhibited good cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer), with IC50 values in low micromolar range and comparable to that of SAHA. These compounds also comparably inhibited HDACs with IC50 values in sub-micromolar range (0.010-0.131 µM) and some compounds (e.g 5f, IC50, 0.010 µM) were even more potent than SAHA (IC50, 0.025 µM) in HDAC inhibition. Representative compounds 6a and 8a appeared to arrest the SW620 cell cycle at G2 phase and significantly induced both early and late apoptosis of SW620 colon cancer cells. Docking experiments on HDAC2 and HDAC6 isozymes revealed favorable interactions at the tunnel of the HDAC active site which positively contributed to the inhibitory activity of synthesized compound. The binding affinity predicted by docking program showed good correlation with the experimental IC50 values. This study demonstrates that simple 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids are also promising as antitumor agents and HDAC inhibitors and these results should provide valuable information for further design of more potent HDAC inhibitors and antitumor agents.


Subject(s)
Antineoplastic Agents/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Oxazoles/chemistry , Thiazoles/chemistry , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Histone Deacetylase Inhibitors/chemistry , Humans , Hydroxamic Acids/chemistry , Molecular Docking Simulation , Spectrum Analysis/methods , Structure-Activity Relationship
17.
Comb Chem High Throughput Screen ; 23(3): 225-231, 2020.
Article in English | MEDLINE | ID: mdl-32072895

ABSTRACT

BACKGROUND: Halogenated corticosteroids are widely used in medicine, and the global need of these steroidal APIs is estimated to be 40 - 70 tons, annually. Vietnam currently imports the pharmaceutical compounds up to 90%, in particular 100% of steroidal drugs. Currently, industrial production is based on the chemical syntheses of corticosteroids from either 16- dehydropregnenolone acetate (obtained from diosgenin) or androstenedione (obtained from phytosterol). The development of shorter synthetic schemes and more economically feasible technologies is of great significance. Introduction of 1(2)-double bond at the final stages of the corticosteroids synthesis results inpoor yield. 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (tetraene acetate) is a key intermediate in the synthesis of highly active halogenated corticosteroids such as dexamethasone and other halogenated corticosteroids. 21-acetoxypregna-1,4,9(11),16- tetraene-3,20-dione is a key intermediate in the synthesis of dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione. OBJECTIVE: The purpose of this study was the development of an efficient and shorter procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, which is a product of a bio-oxidative degradation of the side chain of phytosterols. METHODS: Pregnane side chain was constructed using cyanohydrin method. For 1(2)- dehydrogenation, selene dioxide was applied for the introduction of Δ1(2)-double bond. Other stages of the synthesis were epimerization, Stork's iodination procedure and dehydration. RESULT: 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione was prepared from 9α- hydroxyandrostenedione in yield more than 46%. CONCLUSION: An efficient and practically feasible procedure for the synthesis of 21-acetoxypregna- 1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, a key intermediate for the synthesis of 9-haloidated corticoids, has been developed. The procedure can be applied for the production of value-added 9-haloidated corticoids.


Subject(s)
Androstenedione/chemistry , Hydrogenation , Molecular Conformation , Stereoisomerism
18.
Int J Ment Health Syst ; 13: 57, 2019.
Article in English | MEDLINE | ID: mdl-31462907

ABSTRACT

BACKGROUND: Dementia poses a serious threat to the wellbeing of the elderly. In the context of the rapidly ageing population of Vietnam however, little is known about the prevalence of symptoms and other related factors. This study aims to detect the prevalence of cognitive symptoms of dementia in the elderly in Vietnam as well as other associated factors. METHODS: A cross-sectional study was conducted over a period of six communes at the Northern, Central and Southern region of Vietnam. Prevalence of cognitive symptoms of dementia was the outcome of interest and assessed by Mini Mental State Evaluation (MMSE) questionnaire and was standardized according to the age structure of Vietnam. A total of 3308 adults aged 60 and above were included. Association between having cognitive symptoms of dementia and other factors was assessed with logistic regression. FINDINGS: Cognitive symptoms of dementia were perceived in 46.4% of the sample group. The symptoms were more common among participants who were older, female, had a lower educational level, were not physically active or have previously had stroke. CONCLUSIONS: Prevalence of cognitive symptoms of dementia in adults aged 60 and above was relatively high in Vietnam. Other modifiable associated factors including physical inactivity and social connectedness should also be considered in designing intervention program to prevent dementia in the future.

19.
Anticancer Agents Med Chem ; 19(12): 1543-1557, 2019.
Article in English | MEDLINE | ID: mdl-31267876

ABSTRACT

BACKGROUND: Target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development worldwide, and Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating 6-hydroxy-2 methylquinazolin-4(3H)-ones (14a-m) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2 (liver cancer), MCF-7 (breast cancer) and SKLu-1 (lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships. ADME-T predictions for selected compounds were also performed to predict some important features contributing to the absorption profile of the present hydroxamic derivatives. RESULTS: It was found that the N-hydroxyheptanamide 14i and 14j were the most potent, both in terms of HDAC inhibition and cytotoxicity. These compounds displayed up to 21-71-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in terms of cytotoxicity, and strong inhibition against the whole cell HDAC enzymes with IC50 values of 7.07-9.24µM. Docking experiments on HDAC2 isozyme using Autodock Vina showed all compounds bound to HDAC2 with relatively higher affinities (from -7.02 to -11.23 kcal/mol) compared to SAHA (-7.4 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward breast cancer cells (MCF-7) than liver (HepG2), and lung (SKLu-1) cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Histone Deacetylase 2/antagonists & inhibitors , Histone Deacetylase Inhibitors/pharmacology , Quinazolines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Histone Deacetylase 2/metabolism , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/chemistry , Humans , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Quinazolines/chemistry , Structure-Activity Relationship
20.
Article in English | WPRIM (Western Pacific) | ID: wpr-762127

ABSTRACT

@#Abstract Objective: The World Health Organization’s guidelines on viral hepatitis testing and treatment recommend prioritizing high prevalence groups. Hepatitis C virus (HCV) infection disproportionately affects people who inject drugs and men who have sex with men, but data on female sex workers (FSW) are limited. The study aimed to determine active HCV infection and risk factors associated with HCV exposure among Vietnamese FSW. Methods: We surveyed 1886 women aged ≥ 18 years from Haiphong, Hanoi and Ho Chi Minh City who had sold sex in the last month. We tested for HCV antibody and HCV core antigen as markers for exposure to HCV and active infection, respectively. Results: Across these provinces, high prevalence of HCV exposure (8.8–30.4%) and active infection (3.6–22.1%) were observed. Significant associations with HCV exposure were HIV infection (aOR = 23.7; 95% CI: 14.8–37.9), injection drug use (aOR = 23.3; 95% CI: 13.1–41.4), history of compulsory detention (aOR = 2.5; 95% CI: 1.4–4.2) and having more than 10 sex clients in the last month (aOR = 1.9; 95% CI: 1.2–3.2). Among FSW who reported never injecting drugs, HIV infection (aOR = 24.2; 95% CI: 14.8–39.4), a history of non-injection drug use (aOR = 3.3, CI: 1.8–5.7), compulsory detention (aOR = 2.2; 95% CI: 1.2–4.0) and having over 10 sex clients in the last month (aOR = 2.2, 95% CI: 1.3–3.7) were independently associated with HCV exposure. Discussion: FSW have elevated HCV risks through sex- and drug-related pathways. These findings highlight the need to offer FSW-targeted HCV interventions and ensure their access to HIV prevention and treatment.

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