64 research outputs found
Pyrazoles and Pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazines II
in Wiley Online Library (wileyonlinelibrary.com). Synthesis of the title compounds was achieved using the anils 2a-e and 5a-c derived from the 4-aminopyrazole 1 as starting materials. These compounds were allowed to react with mercaptoacetic acid in boiling dry benzene to afford the corresponding thiazolidinones and spiro-thiazolidinones 3a-e and 6a-c, respectively. Pictet-Spengler reaction of the 4-aminopyrazole hydrochloride 7 with aromatic aldehydes and cyclic ketones resulted in the formation of new pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazines 8a-e and 9a,b, respectively. Other derivatives of pyrazolo pyrrolopyrazines 10 and 11 were obtained via the reaction of the amino derivative 1 with 1,1 0 -carbonyldiimidazol and CS 2 , respectively
An Update of Carbazole Treatment Strategies for COVID-19 Infection
The Coronavirus disease 2019 (COVID-19) outbreak was declared by the World Health
Organization (WHO) in March 2020 to be a pandemic and many drugs used at the beginning proved
useless in fighting the infection. Lately, there has been approval of some new generation drugs for the
clinical treatment of severe or critical COVID-19 infections. Nevertheless, more drugs are required to
reduce the pandemic’s impact. Several treatment approaches for COVID-19 were employed since the
beginning of the pandemic, such as immunomodulatory, antiviral, anti-inflammatory, antimicrobial
agents, and again corticosteroids, angiotensin II receptor blockers, and bradykinin B2 receptor
antagonists, but many of them were proven ineffective in targeting the virus. So, the identification of
drugs to be used effectively for treatment of COVID-19 is strongly needed. It is aimed in this review
to collect the information so far known about the COVID-19 studies and treatments. Moreover, the
observations reported in this review about carbazoles as a treatment can signify a potentially useful
clinical application; various drugs that can be introduced into the therapeutic equipment to fight
COVID-19 or their molecules can be used as the basis for designing new antivirals
Carbazoles: Role and Functions in Fighting Diabetes
Carbazole derivatives have gained a lot of attention in medicinal chemistry over the
last few decades due to their wide range of biological and pharmacological properties, including
antibacterial, antitumor, antioxidant, and anti-inflammatory activities. The therapeutic potential of
natural, semi-synthetic or synthetic carbazole-containing molecules has expanded considerably owing
to their role in the pathogenesis and development of diabetes. Several studies have demonstrated
the ability of carbazole derivatives to reduce oxidative stress, block adrenergic hyperactivation,
prevent damage to pancreatic cells and modulate carbohydrate metabolism. In this survey, we
summarize the latest advances in the synthetic and natural carbazole-containing compounds involved
in diabetes pathways
Metal Complexes with Schiff Bases: Data Collection and Recent Studies on Biological Activities
Metal complexes play a crucial role in pharmaceutical sciences owing to their wide and
significant activities. Schiff bases (SBs) are multifaceted pharmacophores capable of forming chelating
complexes with various metals in different oxidation states. Complexes with SBs are extensively
studied for their numerous advantages, including low cost and simple synthetic strategies. They
have been reported to possess a variety of biological activities, including antimicrobial, anticancer,
antioxidant, antimalarial, analgesic, antiviral, antipyretic, and antidiabetic ones. This review summarizes
the most recent studies on the antimicrobial and antiproliferative activities of SBs-metal
complexes. Moreover, recent studies regarding mononuclear and binuclear complexes with SBs are
described, including antioxidant, antidiabetic, antimalarial, antileishmanial, anti-Alzheimer, and
catecholase activities
N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N-heterocyclic carbene (NHC) complexes [(NHC)(2)Ag](+)[AgX2](-) (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF-7 and MDA-MB-231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram-positive/negative bacteria. These dual properties provide a two-tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents
Antitrypanosomatid Pharmacomodulation at Position 3 of the 8-Nitroquinolin-2(1H)-one Scaffold Using Palladium-Catalysed Cross-Coupling Reactions
International audienceAn antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecule 3-bromo-8-nitroquinolin-2(1H)-one was conducted. Twenty-four derivatives were synthesised using the Suzuki-Miyaura cross-coupling reaction and evaluated in vitro on both Leishmania infantum axenic amastigotes and Trypanosoma brucei brucei trypomastigotes. Introduction of a para-carboxyphenyl group at position 3 of the scaffold led to the selective antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1H)-one (21) with a lower reduction potential (-0.56 V) than the initial hit (-0.45 V). Compound 21 displays micromolar antitrypanosomal activity (IC50 =1.5 μm) and low cytotoxicity on the human HepG2 cell line (CC50 =120 μm), having a higher selectivity index (SI=80) than the reference drug eflornithine. Contrary to results previously obtained in this series, hit compound 21 is inactive toward L. infantum and is not efficiently bioactivated by T. brucei brucei type I nitroreductase, which suggests the existence of an alternative mechanism of action
Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.
BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112
Global economic burden of unmet surgical need for appendicitis
Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US 73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was 75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially
Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy
Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe
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