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Drug Design, Development and Therapy 2021Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological... (Review)
Review
Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.
Topics: Animals; Chemistry, Pharmaceutical; Dihydropyridines; Drug Design; Drug Development; Humans; Pyridines; Structure-Activity Relationship
PubMed: 34675489
DOI: 10.2147/DDDT.S329547 -
Scientific Reports Feb 2022Macromolecular protein crystallisation was one of the potential tools to accelerate the biomanufacturing of biopharmaceuticals. In this work, it was the first time to...
Macromolecular protein crystallisation was one of the potential tools to accelerate the biomanufacturing of biopharmaceuticals. In this work, it was the first time to investigate the roles of biotemplates, Saccharomyces cerevisiae live cells, in the crystallisation processes of lysozyme, with different concentrations from 20 to 2.5 mg/mL lysozyme and different concentrations from 0 to 5.0 × 10 (cfu/mL) Saccharomyces cerevisiae cells, during a period of 96 h. During the crystallisation period, the nucleation possibility in droplets, crystal numbers, and cell growth and cell density were observed and analysed. The results indicated the strong interaction between the lysozyme molecules and the cell wall of the S. cerevisiae, proved by the crystallization of lysozyme with fluorescent labels. The biotemplates demonstrated positive influence or negative influence on the nucleation, i.e. shorter or longer induction time, dependent on the concentrations of the lysozyme and the S. cerevisiae cells, and ratios between them. In the biomanufacturing process, target proteins were various cells were commonly mixed with various cells, and this work provides novel insights of new design and application of live cells as biotemplates for purification of macromolecules.
Topics: Biopharmaceutics; Cell Wall; Crystallization; Fluorescent Dyes; Macromolecular Substances; Muramidase; Saccharomyces cerevisiae
PubMed: 35194113
DOI: 10.1038/s41598-022-06999-7 -
PloS One 2022Poisonous plants cause tremendous economic losses to the livestock industry. These economic losses are deterioration in their health, decreased productivity, deformed...
Poisonous plants cause tremendous economic losses to the livestock industry. These economic losses are deterioration in their health, decreased productivity, deformed offspring, and reduced longevity. The current study is the first comprehensive report on poisonous plants of Azad Jammu and Kashmir which systematically documents the phytotoxicological effect and mode of action in livestock. The information was gathered from 271 informants including 167 men and 104 women through semi-structured interviews and literature search through available databases. The data collected through interviews was analyzed with quantitative tools viz. the factor informant consensus and fidelity level. A total of 38 species of flowering plants belonging to 23 families and 38 genera were reported. Family Asteraceae (5 spp) was the most dominant, followed by Solanaceae (4 spp), Fabaceae (4 spp), Euphorbiaceae (4 spp) and Convolvulaceae (3 spp). Among all the species collected, herbs were the dominant life form (22 spp, 57.89%), trailed by shrubs (11 spp, 28.95%), and trees (5 spp, 13.16%). Whole plant toxicity was reported to be the highest (15 spp, 39.47%), followed by leaf toxicity (12 spp, 31.58%), seed toxicity (4 spp, 7.89%), fruit toxicity (3 spp, 10.53%), latex toxicity (2 spp, 5.26%), flowers toxicity (1 spp, 2.63%), and berries toxicity (1 spp, 2.63%). The most toxic route of administration was found oral (39 spp, 40.63%), followed by intraperitoneal (24 spp, 25%), and intravenous (21 spp, 21.88%). The most commonly affected organ was found liver (20.41%), followed by gastrointestinal tract (20.341%), CNS (16.33%), skin (14.29%), kidneys (12.24%), lungs (4.04%), reproductive organs (2.04%), spleen (1.75%), blood (1.75%), heart (1.75%), urinary tract (1.75%), and pancreas (1.75%). The maximum Fic value was found for dermatological disorders (0.91), followed by the endocrine system (0.90), gastrointestinal (0.82), neurology (0.77), nephrology (0.67), cardiovascular (0.67), urinary (0.67), respiratory (0.60), sexual (0.60) disorders. Senecio vulgaris, and Ageratum conyzoides were the most important plants with fidelity level (0.95) and (0.87). Nerium oleander, Lantana camara, Leucaena leucocephala, and Ricinus communis were the important poisonous plant with maximum fidelity level (100%). Ricinus communis with reported lowest LD50 (<20 mg/kg) was the top-ranked poisonous plant followed by Lantana camara and Justicia adhatoda (25-50 mg/kg), Nerium Oleander (157.37 mg/kg), and Datura innoxia (400 mg/kg). We found that knowledge about poisonous plants is less prevailing in the rural areas of Azad Kashmir compared to the knowledge about medicinal plants and poisonous nature of reported plants is due to production of toxic substances and presence of essential oils.
Topics: Ethnobotany; Ethnopharmacology; Fabaceae; Female; Humans; Knowledge; Lantana; Male; Medicine, Traditional; Nerium; Phytotherapy; Plants, Medicinal; Plants, Toxic; Ricinus
PubMed: 35544538
DOI: 10.1371/journal.pone.0263605 -
Mediators of Inflammation 2016Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress... (Review)
Review
Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.
Topics: Animals; Biological Products; Herbal Medicine; Humans; Inflammation; Lung Diseases
PubMed: 27445433
DOI: 10.1155/2016/2348968 -
Genome Biology and Evolution Dec 2023Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals....
Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes-genes responsible for the processing of exogenous substances such as food, pollutants, and medications-as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.
Topics: Animals; Humans; Neanderthals; Pharmacogenetics; Genome, Human; Hominidae; Biological Evolution
PubMed: 38051947
DOI: 10.1093/gbe/evad222 -
Frontiers in Pharmacology 2023Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the... (Review)
Review
Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the chemical compounds, there is little research about the functions of other contents in medicinal plants. Extracellular vesicles (EVs) are functionally active, nanoscale, membrane-bound vesicles secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular vesicles (PDEVs) also have been implicated to play an important role in therapeutic application. PDEVs were reported to have physical and chemical properties similar to mammalian EVs, which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. Besides these properties, PDEVs also exhibit unique advantages, especially intrinsic bioactivity, high stability, and easy absorption. PDEVs were found to be transferred into recipient cells and significantly affect their biological process involved in many diseases, such as inflammation and tumors. PDEVs also could offer unique morphological and compositional characteristics as natural nanocarriers by innately shuttling bioactive lipids, RNA, proteins, and other pharmacologically active substances. In addition, PDEVs could effectively encapsulate hydrophobic and hydrophilic chemicals, remain stable, and cross stringent biological barriers. Thus, this study focuses on the pharmacological action and mechanisms of PDEVs in therapeutic applications. We also systemically deal with facets of PDEVs, ranging from their isolation to composition, biological functions, and biotherapeutic roles. Efforts are also made to elucidate recent advances in re-engineering PDEVs applied as stable, effective, and non-immunogenic therapeutic applications to meet the ever-stringent demands. Considering its unique advantages, these studies not only provide relevant scientific evidence on therapeutic applications but could also replenish and inherit precious cultural heritage.
PubMed: 38108066
DOI: 10.3389/fphar.2023.1272241 -
British Journal of Pharmacology Aug 2008The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT... (Review)
Review
The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.
Topics: Animals; Hallucinogens; History, 20th Century; Humans; Lysergic Acid Diethylamide; Mental Disorders; Neuropharmacology; Research Design; Serotonin; Serotonin Agents; United Kingdom
PubMed: 18516072
DOI: 10.1038/bjp.2008.207 -
Molecules (Basel, Switzerland) Feb 2023Due to their robust antioxidant capabilities, potential health benefits, wide variety of biological activities, and strong antioxidant qualities, phenolic compounds are... (Review)
Review
Due to their robust antioxidant capabilities, potential health benefits, wide variety of biological activities, and strong antioxidant qualities, phenolic compounds are substances that have drawn considerable attention in recent years. The main goal of the review is to draw attention to saharian Algerian medicinal plants and the determination of their bioactivity (antioxidant, anti-cancer, and anti-inflammatory importance), and to present their chemical composition as well as in vivo and in vitro studies, clinical studies, and other studies confirming their real impact on human health. Research results have revealed a rich variety of medicinal plants used to treat various disease states in this region. Based on in vivo and in vitro studies, biological activity, and clinical studies, a list of 34 species of desert plants, belonging to 20 botanical families, useful both in preventive actions and in the treatment of neoplastic diseases has been established, and polyphenolic compounds have been identified as key to the health potential of endemic diseases and desert plants. It has been shown that people who follow a diet rich in polyphenols are less prone to the risk of many cancers and chronic diseases, such as obesity and diabetes. In view of the increasing antioxidant potential of these plant species, as well as the increasing trade in herbal products from the Sahara region, phytosanitary and pharmaceutical regulations must change in this respect and should be in line with Trade Related Aspects of Intellectual Property Rights (TRIPS), and the sustainable use and development of plant products must be addressed at the same time.
Topics: Humans; Ethnopharmacology; Ethnobotany; Phytotherapy; Algeria; Antioxidants; Plants, Medicinal; Phytochemicals; Plant Extracts
PubMed: 36838819
DOI: 10.3390/molecules28041834 -
Biomolecules Oct 2021This review presents the main patterns of synthesis for theranostics platforms. We examine various approaches to the interpretation of theranostics, statistics of... (Review)
Review
This review presents the main patterns of synthesis for theranostics platforms. We examine various approaches to the interpretation of theranostics, statistics of publications drawn from the PubMed database, and the solid-state and medicinal chemistry methods used for the formation of nanotheranostic objects. We highlight and analyze chemical methods for the modification of nanoparticles, synthesis of spacers with functional end-groups, and the immobilization of medicinal substances and fluorophores. An overview of the modern solutions applied in various fields of medicine is provided, along with an outline of specific examples and an analysis of modern trends and development areas of theranostics as a part of personalized medicine.
Topics: Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Precision Medicine; Theranostic Nanomedicine
PubMed: 34680176
DOI: 10.3390/biom11101544 -
The AAPS Journal Mar 2006Pharmacogenetics/pharmacogenomics is the study of how genetic variation affects pharmacology, the use of drugs to treat disease. When drug responses are predicted in... (Review)
Review
Pharmacogenetics/pharmacogenomics is the study of how genetic variation affects pharmacology, the use of drugs to treat disease. When drug responses are predicted in advance, it is easier to tailor medications to different diseases and individuals. Pharmacogenetics provides the tools required to identify genetic predictors of probable drug response, drug efficacy, and drug-induced adverse events-identifications that would ideally precede treatment decisions. Drug abuse and addiction genetic data have advanced the field of pharmacogenetics in general. Although major findings have emerged, pharmacotherapy remains hindered by issues such as adverse events, time lag to drug efficacy, and heterogeneity of the disorders being treated. The sequencing of the human genome and high-throughput technologies are enabling pharmacogenetics to have greater influence on treatment approaches. This review highlights key studies and identifies important genes in drug abuse pharmacogenetics that provide a basis for better diagnosis and treatment of drug abuse disorders.
Topics: Genetic Variation; Humans; Illicit Drugs; Pharmacogenetics; Substance-Related Disorders
PubMed: 16584126
DOI: 10.1208/aapsj080121