Recent synthetic strategies for N-arylation of pyrrolidines: a potential template for biologically active molecules.

The chemistry of nitrogen-containing heterocyclic compounds has been a multifaceted area of research for an extended period due to their varied therapeutic and biological significance. N-Aryl pyrrolidine formed by condensation of aryl group with nitrogen atom of pyrrolidine is present in a wide array of compounds. Various significant activities shown by N-arylated pyrrolidine include anti-Alzheimer, antihypoxic, anticancer, plant activator, analgesic effect, and hepatitis C inhibitor. This review summarizes different synthetic approaches, e.g., transition-metal catalyzed and transition-metal-free synthesis, decarboxylation reaction, reductive amination, nucleophilic cyclization, Ullmann-Goldberg amidation, Buchwald-Hartwig reaction, Chan-Evans-Lam coupling, addition to benzyne, multistep reaction, green synthesis, rearrangement reaction, and multicomponent reaction, to afford the derivatives of N-aryl pyrrolidine. It encompasses synthetic strategies documented from 2015 to 2023.

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds.

The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.

Antidepressants and their metabolites primarily affect lysosomal functions in the marine mussel, Mytilus galloprovincialis.

Antidepressants widely occur as emerging contaminants in marine coastal waters, with concentrations reported in the low ng/L range. Although at relatively lower levels with respect to other pharmaceuticals, antidepressants - fluoxetine (FLX) in particular - have attracted attention because of their striking effects exerted at low doses on marine invertebrates. In this study, the effects of four antidepressants including FLX, sertraline (SER), and citalopram, as members of the selective serotonin reuptake inhibitor (SSRI) class, and venlafaxine (VEN) as a member of the serotonin and norepinephrine reuptake inhibitor (SNRI) class, were evaluated in the mussel Mytilus galloprovincialis. In addition, the effects of two main metabolites of FLX and VEN, i.e., norfluoxetine (NFL) and O-desmethylvenlafaxine (ODV) respectively, were compared to those of the parent compounds. Eight concentrations of each drug (0.5-500 ng/L range) were tested on the early life stage endpoints of gamete fertilization and larval development at 48 h post fertilization (hpf). Egg fertilization was reduced by all compounds, except for VEN. Larval development at 48 hpf was affected by all SSRIs, but not by SNRIs. The above effects were significant but never exceeded 20 % of control values. Adult mussels were exposed in vivo for 7 days to environmental concentrations of the drugs (0.5, 5, and 10 ng/L) and a battery of eight biomarkers was assessed. Antidepressants primarily targeted lysosomal functions, decreasing haemocyte lysosome membrane stability (up to 70 % reduction) and increasing of the lysosome/cytosol ratio (up to 220 %), neutral lipid (up to 230 %), and lipofuscin (up to 440 %) accumulation in digestive gland. Only SER and NFL significantly affected catalase and glutathione-S-transferase activities in gills and digestive gland. NFL and ODV, were effective and sometimes more active than the parent compounds. All compounds impaired mussel health status, as indicated by the low to high stress levels assigned using the Mussel Expert System.

A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2-the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins-were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Lingual Nerve Injury During Impacted Mandibular Third Molar Surgery.

OBJECTIVE: To determine the frequency of lingual nerve injury (LNI) during the surgical removal of mandibular third molar and the associated risk factors. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Oral and Maxillofacial Surgery, Ayub Teaching Hospital, Abbottabad, from January to June 2021. METHODOLOGY: A total of 121 patients were included in this study who had undergone impacted third molar surgery. Data were collected on a proforma via interview. Patients were followed up after 1 week, 1 month, and 3 months of duration. Frequency of LNI and its association with various surgical procedure steps were determined. RESULTS: This study shows that out of 121 patients, frequency of LNI was found to be 3.3% (n=4). The type of impaction (p=0.047), lingual flap retraction (p<0.001), tooth splitting (p=0.029), and longer duration of surgery were found to be significantly associated with it. CONCLUSION: The frequency of LNI during mandibular impacted third molar surgery was 3.3% in this study, and significantly associated with horizontal impaction, lingual flap retraction, tooth splitting, and duration of surgery longer than 30 minutes. KEY WORDS: Lingual nerve injury, Tooth, Impaction, Third molar, Lingual flap retraction, Tooth splitting.

Recent synthetic approaches towards thienothiophenes: a potential template for biologically active compounds.

Heterocyclic compounds are attractive candidates because of their vast applications in natural and physical sciences. Thienothiophene (TT) is an annulated ring of two thiophene rings with a stable and electron-rich structure. Thienothiophenes (TTs) fully represent the planar system, which can drastically alter or improve the fundamental properties of organic, π-conjugated materials when included into a molecular architecture. These molecules possessed many applications including, pharmaceutical as well as optoelectronic properties. Different isomeric forms of thienothiophene showed various applications such as antiviral, antitumor, antiglaucoma, antimicrobial, and as semiconductors, solar cells, organic field effect transistors, electroluminiscents etc. A number of methodologies were adopted to synthesize thienothiophene derivatives. In this review, we have addressed different synthetic strategies of various isomeric forms of thienothiophene that have been reported during last seven years, i.e., 2016-2022.

Treatment of periodontal disease in pregnancy for the prevention of adverse pregnancy outcomes: a systematic review of systematic reviews.

OBJECTIVE: To assess the systematic reviews and meta-analyses investigating whether or not periodontal treatment in pregnancy was effective in reducing the adverse pregnancy outcomes of preterm birth, low birth weight, preterm low birth weight, stillbirth, foetal growth restriction, and pre-eclampsia. METHODS: The umbrella review was conducted on May 30, 2021, and comprised search of electronic databases MEDLINE, EMBASE, Cochrane Database of Systematic Reviews via Ovid and CINAHL via EBSCO for all systematic reviews and meta-analyses, regardless of the publication date, of randomised controlled trials which investigated the effects of periodontal treatment during pregnancy in preventing or reducing the frequency of at least one adverse pregnancy outcome. The selected studies were subjected to quality assessment and narrative synthesis. RESULTS: Of the 110 studies found, 17(15.5%) met the inclusion criteria. Of them, quality assessment was high for 1(5.9%), moderate 14(82.3%), and low 2(11.8%). A total of 8(47%) studies demonstrated an association with low birth weight, 7(41.2%) with preterm birth, 3(17.6%) with preterm low birth weight, 1(5.9%) with small for gestational age, and 1(5.9%) with stillbirth, while no study demonstrated any association with pre-eclampsia. CONCLUSIONS: Differential findings provided unclear evidence, but periodontal therapy in pregnancy is still recommended as it causes no harm and reduces the bacterial burden in periodontal disease.

Bioplastic leachates characterization and impacts on early larval stages and adult mussel cellular, biochemical and physiological responses.

Bioplastics are promoted as safer alternatives to tackle the long-term persistence of conventional plastics. However, information on the potential release of additives and non-intentionally added substances (NIAS) in the surrounding environment is limited, and biological effects of the leachates have been little studied. Leachates produced from three bioplastics, i.e. compostable bags (CB), bio-polyethylene terephthalate bottles (bioPET) and polylactic acid cups (PLA), and a control polymeric material, i.e. rubber tire (TR), were examined. The chemical nature of bioplastic polyesters PET, PLA and poly (butylene adipate-co-terephthalate) (PBAT) in CB, was confirmed by analytical pyrolysis. Fragments were incubated in artificial sea water for 14 days at 20 °C in darkness and leachate contents examined by GC-MS and HPLC-MS/MS. Catalysts and stabilizers represented the majority of chemicals in TR, while NIAS (e.g. 1,6-dioxacyclododecane-7,12-dione) were the main components of CB. Bisphenol A occurred in all leachates at a concentration range 0.3-4.8 µg/L. Trace metals at concentrations higher than control water were found in all leachates, albeit more represented in leachates from CB and TR. A dose response to 11 dilutions of leachates (in the range 0.6-100%) was tested for biological effects on early embryo stages of Mytilus galloprovincialis. Embryotoxicity was observed in the whole range of tested concentrations, the magnitude of effect depending on the polymers. The highest concentrations caused reduction of egg fertilization (CB, bioPET, TR) and of larvae motility (CB, PLA, TR). TR leachates also provoked larvae mortality in the range 10-100%. Effects on adult mussel physiology were evaluated after a 7-day in vivo exposure to the different leachates at 0.6% concentration. Nine biomarkers concerning lysosomal functionality, neurotransmission, antioxidant and immune responses were assessed. All lysosomal parameters were affected, and serum lysozyme activity inhibited. Harmonized chemical and biological approaches are recommended to assess bioplastic safety and support production of sustainable bioplastics.

Correlation coefficients for T-spherical fuzzy sets and their applications in pattern analysis and multi-attribute decision-making.

T-spherical fuzzy set is an effective tool to deal with vagueness and uncertainty in real-life problems, especially in a situation when there are more than two circumstances, like in casting a ballot. The correlation coefficient of T-spherical fuzzy sets is a tool to calculate the association of two T-spherical fuzzy sets. It has several applications in various disciplines like science, management, and engineering. The noticeable applications incorporate pattern analysis, decision-making, medical diagnosis, and clustering. The aim of this article is to introduce some correlation coefficients for T-spherical fuzzy sets with their applications in pattern recognition and decision-making. The under discussion correlation coefficients are far more advantageous than the existing and many other tools used for T-spherical fuzzy sets, because they are used completely and demonstrate the nature as well as the limit of association between two T-spherical fuzzy sets. Further, an application of proposed correlation coefficients in pattern analysis is discussed here. In addition to it, the proposed correlation coefficients are applied to a multi-attribute decision-making problem, in which the selection of a suitable COVID-19 mask is presented. A comparative analysis has also been made to check the effectiveness of the proposed work with the existing correlation coefficients.

Control analysis of virotherapy chaotic system.

In this work, we consider a chaotic system that plays a vital role in the treatment of cancer by injection of a virus externally. Due to the sensitivity of this disease, most of its treatments are highly risky. Therefore, we have designed control inputs using adaptive and passive control techniques for virotherapy. Both controllers are designed to bring global stability to the cancer system with the aid of a quadratic Lyapunov function. Furthermore, we use simulations to verify our controllers. Moreover, we show that our adaptive control technique gives better results in comparison.