Antimalarial Chloroquine Research Articles

Designing a molecularly imprinted polymer-based electrochemical sensor for the sensitive and selective detection of the antimalarial chloroquine phosphate

Designing a molecularly imprinted polymer-based electrochemical sensor for the sensitive and selective detection of the antimalarial chloroquine phosphate

Consumer Behavior Analysis as a Form of Pre-market Survey for the Black Pule (Alstonia spectabilis) Antimalarial Tablet Prototype

Background: Malaria a disease caused by the protozoan parasite Plasmodium with a high incidence of spread that is still found in remote tropical places, especially areas around gardens, swamps, forests, and mines such as eastern Indonesia. The commonly used antimalarial drug chloroquine has experienced resistance, encouraging researchers to look for effective alternative treatments. Formulation development of Standardized Herbal Medicine (OHT) from black pule was carried out as a potential new alternative treatment as an antimalarial. Objectives: The purpose of this study was to determine the level of liking and quality assessment or characteristics of the prototype of antimalarial OHT tablets. Methods: The method used in this research is descriptive quantitative which aims to describe the panelists' perspective on the product and to analyze product marketing. In this research method includes hedonic test and hedonic quality test which is a series of organoleptic tests and consumer acceptance tests by tasting and observing the product followed by filling out a form according to what is felt and observed. Results: The results obtained from this research, namely the preference test of the overall characteristics of the prototype of antimalarial black pule tablets (Alstonia spectabilis) showed a good sensory impression and characteristics. The positive results obtained from all aspects have illustrated that the panelists have considerable interest in the prototype sample and assess that the prototype tablets are suitable for dissemination to the public. Conclusions: Based on the research, it can be concluded that the prototype of black pule (Alstonia spectabilis) tablets tested through hedonic and hedonic quality tests produced overall good results, characterized by the tendency of panelists to choose "Like" in the hedonic test of sensory impressions and positive values in the hedonic quality test.

Recent Innovations in Synthetic Methodologies and Patent Landscape of Quinoline Analogues: A Comprehensive Review

: Quinoline is a general group of heterocyclic compounds that have garnered much interest in medicinal chemistry and drug development due to their wide range of pharmacological effects. Pyridine ring fused with benzene defines the class of chemical compounds known as quinolines. Quinoline is a weak tertiary base, also known as 1-aza-naphthalene. Numerous patents have been filed for the synthesis of quinoline-based compounds, discussing about their derivatives and uses. Here, we have discussed the methods of quinoline synthesis, structural alterations, and patents showing its importance in various industries. Quinolines have been investigated as antimalarial substances, with substances, like quinine and chloroquine, serving as notable examples, and they have also been investigated to possess anti-inflammatory, anti-tumor, and CNS activity. The synthesis of quinoline is also subjected to several recognized procedures. The variations in the ring system and various synthetic approaches are the key highlights of the article, and it includes the various catalysts that could be recycled and reused by the assisted technique, which increases the yield and requires less time for the synthesis (ultrasound-promoted synthesis, one-pot reaction, and microwave and photocatalytic reactions). The development of synthetic procedures can help in the sustainable synthesis of quinoline derivatives.

Amodiaquine Nonspecifically Binds Double Stranded and Three-Way Junction DNA Structures.

The 4-aminoquinoline class of compounds includes the important antimalarial compounds amodiaquine and chloroquine. Despite their medicinal importance, the mode of action of these compounds is poorly understood. In a previous study we observed these compounds, as well as quinine and mefloquine, tightly bind the DNA cocaine-binding aptamer. Here, we further explore the range of nucleic acid structures bound by these compounds. To gauge a wide range of binding affinities, we used isothermal titration calorimetry to explore high affinity binding (nM to tens of μM) and NMR spectroscopy to assay weak binding biding in the hundreds of micromolar range. We find that amodiaquine tightly binds all double stranded DNA structures explored. Mefloquine binds double stranded DNA duplex molecules tightly and weakly associates with a three-way junction DNA construct. Quinine and chloroquine only weakly bind duplex DNA but do not tightly bind any of the DNA constructs explored. A simulation of the free energy of binding of these ligands to the Dickerson-Drew dodecamer resulted in an excellent agreement between the simulated and experimental free energy. These results provide new insight into the DNA binding of clinically important antimalarial compounds and may play a role in future development of new antimalarials.

Spectrally Resolved and Highly Parallelized Raman Difference Spectroscopy for the Analysis of Drug-Target Interactions between the Antimalarial Drug Chloroquine and Hematin.

Malaria is a severe disease caused by cytozoic parasites of the genus Plasmodium, which infiltrate and infect red blood cells. Several drugs have been developed to combat the devastating effects of malaria. Antimalarials based on quinolines inhibit the crystallization of hematin into hemozoin within the parasite, ultimately leading to its demise. Despite the frequent use of these agents, there are unanswered questions about their mechanisms of action. In the present study, the quinoline chloroquine and its interaction with the target structure hematin was investigated using an advanced, highly parallelized Raman difference spectroscopy (RDS) setup. Simultaneous recording of the spectra of hematin and chloroquine mixtures with varying compositions enabled the observation of changes in peak heights and positions based on the altered molecular structure resulting from their interaction. A shift of (-1.12 ± 0.05) cm-1 was observed in the core-size marker band ν(CαCm)asym peak position of the 1:1 chloroquine-hematin mixture compared to pure hematin. The oxidation-state marker band ν(pyrrole half-ring)sym exhibited a shift by (+0.93 ± 0.13) cm-1. These results were supported by density functional theory (DFT) calculations, indicating a hydrogen bond between the quinolinyl moiety of chloroquine and the oxygen atom of ferric protoporphyrin IX hydroxide (Fe(III)PPIX-OH). The consequence is a reduced electron density within the porphyrin moiety and an increase in its core size. This hypothesis provided further insights into the mechanism of hemozoin inhibition, suggesting chloroquine binding to the monomeric form of hematin, thereby preventing its further crystallization to hemozoin.

In vitro drug interaction of ionophores with artemisinin and chloroquine against Plasmodium falciparum 3D7 blood-stage infection

The prevalence of clinical resistance of P. falciparum towards artemisinin and its partner drugs has significantly hampered malarial chemotherapy. To circumvent this situation, identifying a new class of partner drugs with significant anti-malarial efficacy and multi-stage activity can slow the development of resistance. This study demonstrates the potential interactions of carboxylic ionophores such as monensin (MON), maduramicin (MAD) or salinomycin (SAL) with standard antimalarial drugs artemisinin (ART) or chloroquine (CQ). The in vitro drug interactions were studied in P. falciparum 3D7 strain by a growth inhibition SYBR green 1 assay. The asynchronized parasites were exposed for 48 h in the presence of varying proportions of two drug concentrations using the modified fixed-ratio isobologram method. We determined the growth inhibition response and the sums of the fractional inhibitory concentrations (ΣFICs) of the following drug combinations (4:1, 3:2, 2:3, 1:4) and (1:1, 1:3, 3:1) were calculated for 50% inhibitory concentrations (IC50s). Combining artemisinin with monensin, maduramicin, or salinomycin showed significant additive interaction. A combination of chloroquine with monensin, maduramicin, or salinomycin showed slight synergism to additive interaction. None of the drug combinations displayed an antagonistic effect indicating ionophores usage in combination therapy to treat drug-resistant malarial infections.

Exposures to Bleach, Peroxide, Disinfectants, Antimalarials, and Ivermectin Reported to the California Poison Control System Before and During the COVID-19 Pandemic, 2015-2021.

The COVID-19 pandemic led to widespread fear of infection, with many people expanding their use of cleaning products and trying unproven prevention and treatment strategies. We described shifts in reported exposures related to COVID-19 home interventions. This study considered suspected toxicity exposures involving household cleaning products (bleach, peroxide, disinfectants), antimalarials (hydroxychloroquine and chloroquine), and ivermectin reported to the California Poison Control System from 2015 through 2021 and assessed trends in exposures by using interrupted time-series analyses. We found a significant increase in exposures reported to the California Poison Control System related to household cleaning products and ivermectin during the COVID-19 pandemic. As of January 1, 2015, the baseline level of reported exposures to household cleaning products was 707.33 per month and was declining at a rate of 1.71 (95% CI, -2.87 to -0.56) per month through February 29, 2020. In March 2020, an increase of 466.57 (95% CI, 328.08-605.07) reported exposures above baseline occurred, after which exposures to cleaning products decreased at a rate of 23.40 (95% CI, -32.48 to -14.32) per month. The number of reported exposures to antimalarials did not change significantly before or during the pandemic. The number of reported ivermectin exposures before December 2020 was initially stable at 14.50 per month and then increased by 2.05 per month through December 2021. Our observations suggest that while some dangerous home prevention and treatment efforts resolve over time, further interventions may be needed to reduce the public health effects related to attempts to self-treat COVID-19 with ivermectin.

Ferrocene-Based Drugs, Delivery Nanomaterials and Fenton Mechanism: State of the Art, Recent Developments and Prospects.

Ferrocene has been the most used organometallic moiety introduced in organic and bioinorganic drugs to cure cancers and various other diseases. Following several pioneering studies, two real breakthroughs occurred in 1996 and 1997. In 1996, Jaouen et al. reported ferrocifens, ferrocene analogs of tamoxifen, the chemotherapeutic for hormone-dependent breast cancer. Several ferrocifens are now in preclinical evaluation. Independently, in 1997, ferroquine, an analog of the antimalarial drug chloroquine upon the introduction of a ferrocenyl substituent in the carbon chain, was reported by the Biot-Brocard group and found to be active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Ferroquine, in combination with artefenomel, completed phase IIb clinical evaluation in 2019. More than 1000 studies have been published on ferrocenyl-containing pharmacophores against infectious diseases, including parasitic, bacterial, fungal, and viral infections, but the relationship between structure and biological activity has been scarcely demonstrated, unlike for ferrocifens and ferroquines. In a majority of ferrocene-containing drugs, however, the production of reactive oxygen species (ROS), in particular the OH. radical, produced by Fenton catalysis, plays a key role and is scrutinized in this mini-review, together with the supramolecular approach utilizing drug delivery nanosystems, such as micelles, metal-organic frameworks (MOFs), polymers, and dendrimers.

Quantification of Plasmodium falciparum HRP-2 as an alternative method to [3H]hypoxanthine incorporation to measure the parasite reduction ratio in vitro

In the absence of a highly efficacious vaccine, chemotherapy remains the cornerstone to control malaria morbidity and mortality. The threat of the emergence of parasites resistant to artemisinin-based combination therapies highlights the need for new antimalarial drugs ideally with superior properties. The killing rate reflects the speed of action of antimalarial drugs that can be measured in vitro through the parasite reduction ratio (PRR) assay to shortlist interesting candidates. As a standard, the in vitro PRR assay is performed by measuring [3H]hypoxanthine incorporation of Plasmodium falciparum. This methodology is restricted to specialized laboratories due to the handling of radioactive material. In this work, we describe the sandwich enzyme-linked immunosorbent assay to detect P. falciparum histidine-rich protein 2 (HRP-2) as an alternative methodology to assess the PRR. We first validated the methodology with established antimalarial drugs (artesunate, chloroquine, pyrimethamine, and atovaquone) by comparing our results to previous results of the [3H]hypoxanthine incorporation readout provided by an expert lab and subsequently assessed the speed of action of four new antimalarial candidates (compound 22, chlorotonil A, boromycin, and ivermectin). The HRP-2 PRR assay obtained comparable results to the hypoxanthine incorporation readout in terms of parasite growth rate over time, lag phase, and parasite clearance time. In addition, parasite growth following drug exposure was quantified after 7, 14, 21, and 28 days of recovery time. In conclusion, the PRR assay based on HRP-2 is similar to [3H]hypoxanthine in determining a drug´s parasite-killing rate and can be widely used in all research laboratories.

High-efficient degradation of chloroquine phosphate by oxygen doping MoS2 co-catalytic Fenton reaction

To degrade the antiviral and antimalarial drug chloroquine phosphate (CQP), an oxygen doping MoS2 nanoflower (O-MoS2-230) co-catalyst was prepared by a hydrothermal method to construct an O-MoS2-230 co-catalytic Fenton system (O-MoS2-230/Fenton) without pH adjustment (initial pH 5.4). Remarkable CQP degradation efficiency (99.5 %) could be achieved in 10 min under suitable conditions ([co-catalyst] = 0.2 g L–1, [Fe2+]0 = 70 μM, [H2O2]0 = 0.4 mM) with a reaction rate constant of 0.24 min–1, which was 4.8 times that of MoS2 co-catalytic Fenton system (MoS2/Fenton). Compared to MoS2/Fenton, the system had 1.5 times more Fe2+ (28.4 μM) and showed a 24.0 % increase in H2O2 activation efficiency, reaching 50.0 %. The electron paramagnetic resonance (EPR) determinations and active species trapping experimental data revealed that •OH and 1O2 were responsible for CQP degradation. The combination of experiments and density functional theory (DFT) calculation demonstrates that O doping in MoS2 modifies the surface charge distribution, leading to an increase in its conductivity, thus accelerating the Fe3+/Fe2+ cycle and promoting reactive oxygen species (ROS) generation. Furthermore, O-MoS2-230/Fenton system exhibited excellent stability. This work reveals the degradation mechanism of accelerated Fe3+/Fe2+ cycle and abundant ROS in the O-MoS2-230/Fenton system and provides a promising technology for antibiotic pollutant degradation.

Clinical characterization of a cohort of patients treated for systemic lupus erythematosus in Colombia: A retrospective study.

Systemic lupus erythematosus is an autoimmune disease associated with serious complications and high costs. The aim was to describe the clinical characteristics and health care resource utilization of a Colombian systemic lupus erythematosus outpatient cohort. This was a retrospective descriptive study. Clinical records and claims data for systemic lupus erythematosus patients from ten specialized care centers in Colombia were reviewed for up to 12 months. Baseline clinical variables, Systemic Lupus Erythematosus Disease Activity Index, drug use, and direct costs were measured. Descriptive statistics were analyzed using SPSS. A total of 413 patients were included; 361 (87.4%) were female, and the mean age was 42 ± 14 years. The mean disease evolution was 8.9 ± 6.0 years; 174 patients (42.1%) had a systemic manifestation at baseline, mostly lupus nephritis (105; 25.4%). A total of 334 patients (80.9%) had at least one comorbidity, mainly antiphospholipid syndrome (90; 21.8%) and hypertension (76; 18.4%). The baseline Systemic Lupus Erythematosus Disease Activity Index score was 0 in 215 patients (52.0%), 1-5 in 154 (37.3%), 6-10 in 41 (9.9%) and 11+ in 3 (0.7%). All patients received pharmacological therapy, and the most common treatment was corticosteroids (293; 70.9%), followed by antimalarials (chloroquine 52.5%, hydroxychloroquine 31.0%), immunosuppressants (azathioprine 45.3%, methotrexate 21.5%, mycophenolate mofetil 20.1%, cyclosporine 8.0%, cyclophosphamide 6.8%, leflunomide 4.8%) and biologicals (10.9%). The mean annual costs were USD1954 per patient/year, USD1555 for antirheumatic drugs (USD10,487 for those with biologicals), USD86 for medical visits, USD235 for drug infusions and USD199 for laboratory tests. Systemic lupus erythematosus generates an important economic and morbidity burden for the Colombian health system. Systemic lupus erythematosus outpatient attention costs in the observation year were mainly determined by drug therapy (especially biologics), medical visits and laboratory tests. New studies addressing the rate of exacerbations, long-term follow-up or costs related to hospital care are recommended.

Susceptibility of Southeast Asian Plasmodium falciparum isolates to P218

A major threat to the goal of eliminating malaria, particularly in Southeast Asia, is the spread of Plasmodium falciparum resistant to artemisinin-based combination therapies. P218 is a drug candidate designed to combat antifolate-sensitive and -resistant parasites. However, there is no evidence that P218 is effective against artemisinin-resistant P. falciparum. This report investigated the susceptibilities of 10 parasite isolates from Southeast Asia to P218 and other antimalarial drugs. All isolates with different levels of artemisinin resistance were genetically distinct from one another, although common haplotypes associated with antimalarial resistance were identified. All isolates were highly resistant to pyrimethamine, and none of them were significantly less sensitive to P218 than the pyrimethamine-resistant laboratory strain V1/S. Significant differences in sensitivity to other types of antimalarials (mefloquine, atovaquone and chloroquine) compared with V1/S were found for some isolates, although the differences were not clinically relevant. P218 is thus efficacious against multi-drug (including artemisinin-resistant P. falciparum.

Synthesis of novel 2- and 8-substituted 4-amino-7-chloroquinolines and their N-alkylated coupling products

The synthesis of a series of 2- and 8-substituted 4-amino-7-chloroquinolines is presented. Starting from 4,7-dichloroquinolines, the chloro in the 4-position can be effectively substituted using amino alcohols to yield novel analogues of the antimalarial (hydroxy)chloroquine. Both short-chain (2-aminoethanol) and long-chain (5-[ N-ethyl- N-(2-hydroxyethyl)amino]-2-aminopentane) coupling partners can be used. While ketone and nitro functionalities were found to be incompatible with the coupling conditions, electron-donating amino and dimethylamino substituents were tolerated. In addition to characterization in solution using multinuclear NMR spectroscopy and high-resolution mass spectrometry, single-crystal X-ray structures are presented of two 4,7-dichloroquinolines as well as three of the N-alkylated products including a unique species in which a pyrrole heterocycle formed at the 2-position of the quinoline subunit and a rare example of a 4-aza-1,10-phenanthroline.

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA.

Antimalarial action of a drug is closely associated with the interaction with the parasite's DNA. Hence, in this study, the interaction of an important antimalarial drug, chloroquine (CLQ), has been investigated with six different sequences of DNA having pure adenine (A)-thymine (T) and pure cytosine (C)-guanine (G) as well as mixed nucleobases to achieve the nucleobase level of information in the binding of antimalarial drug with DNA along with binding induced stabilization/destabilization of DNA using different spectroscopic methods and molecular dynamics simulation technique. Further, the experiments have been also performed with 4-amino-7-chloroquinoline (7CLQ), an analogue of CLQ, to understand the role of the quinoline ring and side chain of CLQ in the binding with different sequences of DNA. The binding efficiency of CLQ with any sequence of DNA is higher than 7CLQ suggesting that the presence of charge on CLQ plays a prominent role in DNA binding. The data suggest that the binding of drug as well as induced stabilization of DNA depends significantly on the nature as well as the arrangement of the nucleobases. In general, the binding of CLQ with pure CG DNA is higher than with pure AT DNA; moreover, it prefers an alternate order of CG/AT than continual nucleobases in duplex DNA. CLQ predominately accommodates in the minor groove of AT DNA and prefers to form hydrogen bond mostly with the adenine nucleobase. In contrast to AT DNA, CLQ intrudes into the both major and minor grooves, but it is primarily accommodated into the major groove of CG DNA. CLQ forms a hydrogen bond mainly with guanine in the major groove and cytosine in the minor groove of CG DNA which enhances the binding of CLQ compared to AT DNA as well as induces higher stabilization in CG DNA. The molecular level information obtained about the functional group responsible for the interaction of CLQ as well as the role of chemical nature of nucleobases along with its ordering on the binding of CLQ with DNA may be useful in comprehensive understanding of its action mechanism.

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model.

We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.

Optimization of HPLC-MS/MS method for determination of antimalarial adulterants in herbal products.

The use of herbal products is booming all over the world because of being believed as safer than conventional drugs and free of side effects. However, there are untrustworthy manufacturers who adulterate herbal products by adding conventional drugs which might eventually lead to microbial resistance and herb-to-drug interactions. There is a need to develop methods for detecting adulterants in herbal products. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous identification and determination of conventional antimalarials (chloroquine, quinine, sulfadoxine, pyrimethamine, mefloquine, lumefantrine, amodiaquine, artemisinin, dihydroartemisinin, artesunate and artemether) in herbal products was developed. Stable isotopically labelled compounds (artemether-d3, quindine-d3, and sulfadoxine-d3) were used as internal standards (ISs) for quantitative analysis. Extraction of analytes was performed using methanol: water: formic acid (90:10:0.1, v/v) and chromatographic separation was done in a gradient mode using mobile phase A: Ultrapure water containing 0.1% formic acid and 1mM ammonium formate and mobile phase B: Acetonitrile/methanol (50:50) containing 0.1% formic acid and 1mM ammonium formate. The calibration curves were linear (r2 ≥ 0.991) over the range of 0.001-0.3µgmL-1 for all compounds. The limit of detection (LOD) ranged from 0.002 to 0.02μgmL-1 while the limit of quantification (LOQ) ranged from 0.006 to 0.08μgmL-1. Accuracy, expressed as recovery of spiked herbal products ranged from 52 to 128%. The precision, expressed as percent relative standard deviation (%RSD) at two concentration levels, ranged from 1.0 to 13.8%. The matrix effect expressed as the matrix factor (MF) ranged from 0.77 to 0.97. The developed method was used to identify and quantify conventional antimalarials in herbal product samples from Tanzania. Ten out of 50 herbal products were found to contain amodiaquine, sulfadoxine, pyrimethamine, mefloquine, dihydroartemisinin, artemether and lumefantrine. The developed method is considered a valuable tool for getting a better understanding of the adulteration of conventional antimalarials in herbal products.

Adverse events in rheumatoid arthritis patients under antimalarial treatment—Is there cardiovascular compromise?

Introduction: The antimalarials chloroquine and hydroxychloroquine have been used for several decades in treating malaria and some autoimmune diseases—mainly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)—with excellent efficacy and safety. Due to the massive use of antimalarials worldwide for managing SARS-CoV-2/COVID-19 infection during the last 2 years and the consequent increase in cardiac arrhythmia, fear has risen about the safety of using antimalarials, especially for patients with increased cardiovascular risk.Objective: To describe a real-life experience about the safety of antimalarials in the setting of a single rheumatological center in Colombia.Methods: This is a cross sectional study that includes patients diagnosed with RA and treated with antimalarials between 2020 and 2021. Clinical follow-up information was gathered from the medical records, and all reported adverse events were described.Results: A total of 957 patients were included, primarily women (79.2%). The most frequent comorbidities were hypertension and osteoporosis. Chloroquine use was more frequent than hydroxychloroquine (86.4% vs. 13.6%). During the observation period, 243 (25.4%) patients presented at least one adverse event, 72 (29.6%) had retinal toxicity, 85 (35%) dermatological events, and 81 (33.3%) gastrointestinal intolerance. Other adverse events reported less frequently (15.2%) included headache, dizziness, lipothymia, and elevated transaminases. There were no reports of cardiovascular events from the period of antimalarial use to the date of data collection despite the high frequency of previous metabolic or cardiovascular disease in this cohort.Conclusion: This study reasserts the evidence of antimalarials safety profile for patients with rheumatological conditions such as RA. RA patients that were treated with antimalarials at doses recommended by the guidelines had no cardiovascular events.

Understanding the Visible-Light-Initiated Manganese-Catalyzed Synthesis of Quinolines and Naphthyridines under Ambient and Aerobic Conditions

Polyaromatic N-heterocycles are some of the most common building blocks in natural products and active pharmaceutical ingredients. Significant efforts have been devoted to developing catalytic protocols, including those which use an acceptorless dehydrogenation strategy at elevated temperatures, to produce polyaromatic N-heterocycles like quinolines and naphthyridines. However, photoinitiated catalysis driven by visible light offers a milder and often more selective protocol as an alternative to thermal reactions. Here, we present the catalytic syntheses of quinolines and naphthyridines from ortho-aminobenzyl alcohols and ketones using the photocatalyst [Mn(L1H)(CO)3Br] (L1H = 7-hydroxy-2-methyl-1,8-naphthyridine-N-oxide), bearing a phenolic unit on a 1,8-naphthyridine-N-oxide scaffold, under ambient and aerobic conditions with visible light illumination. We describe a broad, functional group-tolerant substrate scope of >30 examples under modest reaction conditions. A variety of 2-aminobenzyl alcohols containing electron-donating and electron-deficient groups and (2-aminopyridin-3-yl)methanol are converted to the corresponding quinolines and naphthyridines using ambient air as an oxidant in the presence of KOH. We synthesized a wide range of derivatives, including some of the bioactive antimalarial drug chloroquine and the steroids progesterone and pregnenolone to highlight the value-added applications of this catalytic protocol for pharmaceutical ingredient and natural product syntheses. We performed substrate viability, ultraviolet–visible, electron paramagnetic resonance, and X-ray photoelectron spectroscopy studies, as well as density functional theory calculations to gain mechanistic insights to the reaction pathway. The catalytic cycle involves condensation of the amino group in the ortho-aminobenzyl alcohol with the ketone initially, which is followed by aerobic oxidation of the benzyl alcohol to the corresponding benzaldehyde catalyzed by the photoinitiator [Mn(L1H)(CO)3Br] in the presence of visible light, and finally, a KOH-promoted condensation and cyclization to afford quinolines as the final products.

Intensified use of chloroquine/hydroxychloroquine and consequences on oral health: A narrative and systematic review

In this article, the objective is to discuss, because of the pandemic resulting from the new Coronavirus (SARS-CoV-2) and the axis was bibliographic research carried out in the field of Dentistry, the intensification of the use of antimalarial drugs chloroquine and hydroxychloroquine and the consequences for the oral health of citizens. The data sources were scientific platforms, books, and texts selected according to their relevance to the theme, seeking to diversify the sources, carefully selected. Data indicate that the main occurrence with an impact on the oral health of these drugs is drug hyperpigmentation. It was also evident that there is a lack of up-to-date studies related to the subject in the field of dentistry, with dentists playing a central role in collaborating to maintain the overall health of patients. It means to say that as in-depth use of these drugs was identified, whose effects impact oral health, more studies must be carried out with this object of study in contemporary times, especially because of the intensification of the use, above all, of chloroquine during the experienced pandemic. It is expected that this study will contribute to those that will be carried out afterward, whether exploratory or in-depth.

Chloroquine modulates the sulforaphane anti-obesity mechanisms in a high-fat diet model: Role of JAK-2/ STAT-3/ SOCS-3 pathway

The phytochemical sulforaphane (SFN) has been studied for its potential anti-obesity effect, but neither its molecular targets nor its interaction with the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, high-fat diet (HFD) obese rats were randomly allocated into one of five groups and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess their potential interaction and the enrolled mechanisms. SFN effectively reduced the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved lipid profile. On the molecular level, SFN inhibited the lipogenesis-related enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory pathway conserved Janus kinase/signaling transducers and activators of transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these tissues, as well as the inflammatory markers nuclear factor-kappa (NF-κ) B and interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression of microRNA (miR-200a), while significantly increasing the autophagic parameters; viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the parameters mentioned above, treatment with CQ solely produced a satisfactory effect and intensified the low dose of SFN in the combination regimen. These findings demonstrated the beneficial effects of using CQ as an add-on anti-obesity medicine to SFN.