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2021 ◽  
Vol 23 (4) ◽  
pp. 107-108
Author(s):  
Richard Robbins ◽  
◽  
Thomas Kummet

No abstract available. Article truncated after 150 words. One aspect of the high cost of healthcare is the cost of new drugs. Cancer drugs have received much of the attention because of their extremely high price (1). For example, crizotinib, used to treat non-small cell lung cancer (NSCLC), costs $19,144 for each month's supply. Pfizer, the manufacturer of crizotinib, has just announced that they are offering a refund if its drug "doesn't work" (2). If crizotinib use is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month's supply, or a total of $57,432. Of course, the cost of care includes more than just a single drug and can be much higher and Pfizer is reimbursing only the drug cost. Although Pfizer claims that its pilot program is a first in the …


Author(s):  
Yingdong Cao ◽  
Hong Lu

Tuberculosis is a deadly communicable disease caused by the bacillus Mycobacterium tuberculosis (MTB), and pulmonary tuberculosis accounts for over 80% of the total cases. The 1,2,4-triazole is a privileged structure in the discovery of new drugs, and its derivatives act on various targets in MTB. In particular, 1,2,4-triazole hybrids can not only exert dual or multiple antitubercular mechanisms of action but also have the potential to enhance efficacy and reduce side effects. The present work aims to summarize the current status of 1,2,4-triazole hybrids as potential antitubercular agents, covering articles published between 2010 and 2020, to aid the further rational design of novel potential drug candidates endowed with higher efficacy, better compliance and fewer side effects.


Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6440
Author(s):  
Viveca Giongo ◽  
Annarita Falanga ◽  
Camilly P. Pires De Melo ◽  
Gustavo B. da Silva ◽  
Rosa Bellavita ◽  
...  

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.


2021 ◽  
Author(s):  
Exequiel Porta ◽  
Shane Wilkinson ◽  
María Sol Ballari ◽  
Babu Tekwani ◽  
Guillermo Labadie

A series of thirty 1,2,3-triazolylsterols were prepared by a stereocontrolled synthesis and inspired by azasterols with proven antiparasitic activity. Ten of these compounds constitute chimeras/hybrids of AZA and 1,2,3-triazolyl azasterols. The entire library was assayed against the etiological agents of the parasites responsible of kinetoplastid diseases (L. donovani, T. cruzi and T. brucei). Several of the compounds were active at submicromolar/nanomolar concentration with excellent selectivity index, when compared to their activity in mammalian cells. Studies of the physicochemical properties in silico were conducted to rationalize the activities.


2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Klaus G. Parhofer

Abstract Purpose of Review For many years, the lipid-lowering armamentarium consisted of statins and/or ezetimibe and/or bile acid sequestrants and/or fibrates. Now, with the availability of new drugs mostly injectables, the field has changed and the role of oral non-statin drugs (including bempedoic acid) must be reevaluated. Recent Findings Ezetimibe remains a very important combination partner for statins with continuously increasing treatment numbers. Bempedoic acid is another interesting combination partner for statin/ezetimibe or ezetimibe alone but lacks in contrast to ezetimibe evidence from outcome trials. The role of fibrates is less clear as they have shown disappointing results in outcome trials but may still be used in selected, high-risk patients with combined dyslipidemia. Bile acid sequestrants are now rarely used as there are stronger, better tolerable ways to lower LDL-cholesterol. Summary With the introduction of new injectable lipid-lowering drugs, some oral drugs such as ezetimibe and bempedoic acid still have an important spot in our treatment algorithm others such as fibrates have a less clear role while again others are now rarely used.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader

Alzheimer’s disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer’s disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes’ target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.


2021 ◽  
Vol 10 (13) ◽  
pp. e301101321482
Author(s):  
Rafael Santos Santana ◽  
Helaine Carneiro Capucho ◽  
Silvana Nair Leite

The "epidemiological transition" has fostered increasing attention to chronic and non-communicable diseases, but neglected diseases are still present and their relationship with the population's socioeconomic inequalities is increasingly evident, so much so that there has been a conceptual conversion to call them “poverty-related diseases”. It is a necessary to review and to discuss the characteristics and challenges of Brazilian pharmaceutical policies for populations affected by diseases related to poverty. This review of the literature was carried out, with works of the last 10 years dealing with the theme and the Brazilian reality. Out of the 272 identified articles, only 43 publications were included in this study. The results were: (i) the difficulties of investing in the research, development and production of new drugs for these diseases; (ii) the characteristics of access policies to medicines already available, their advances and limitations; (iii) and issues related to the right to comprehensive pharmaceutical assistance. Therefore, for the available therapies, national production and federal funding contributed to guarantee the supply. Assisted qualification actions are necessary and little discussed in area studies.


2021 ◽  
pp. 45-51
Author(s):  
А.Б. ДЖУМАГАЗИЕВА ◽  
Е.Н. САХИПОВ ◽  
С. ТУРГАНБАЙ ◽  
Н.М. АТАГЕЛЬДИЕВА ◽  
У.М. ДАТХАЕВ ◽  
...  

Лекарственная устойчивость к антибиотикам вызвала необходимость поиска новых лекарственных средств и лекарственных форм. Известно, что семиорганические аддукты иода обладают широким спектром антимикробного действия. Эти же соединения, содержащие в своем составе молекулу галогена - иода, могут выступать в качестве галогенирующего агента в отношении антибиотиков. Изучено взаимодействие антибиотиков тетрациклина, гентамицина, хлорамфеникола, относящихся к классам поликетидов, аминогликозидов и амфениколов, соответственно, с аддуктом иода методами рефрактометрии, УФ-спектроскопии и ИК-спектроскопии. Показано, что антибиотик хлорамфеникол не взаимодействует с семиорганическим аддуктом иода ди2-аминопропионовой кислоты дитрииодоводород моногидратом (субстанция D1). Antibiotic drug resistance has necessitated the search for new drugs and dosage forms. It is known that semiorganic iodine adducts have a wide spectrum of antimicrobial effects. The same compounds containing a halogen-iodine molecule may act as a antibiotics halogenating agent. The interaction of antibiotics tetracycline, gentamicin, chloramphenicol belonging to the classes of polyketides, aminoglycosides and amphenicols, respectively, with iodine adduct by refractometry, UV spectroscopy and IR spectroscopy was studied. It has been shown that the antibiotic chloramphenicol does not interact with the semiorganic adduct of di-2-aminopropionic acid ditriiodinehydride monohydrate (D1 substance).


Author(s):  
Adela Ngwewondo ◽  
Ivan Scandale ◽  
Sabine Specht

Abstract Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of “old” drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zinar Alan ◽  
Halil Özgüldü ◽  
Meryem Sedef Erdal ◽  
Ayşenur Yaman Bucak ◽  
A. Yağız Üresin ◽  
...  

Abstract Background Ethnobotanical studies investigating a large number of traditional herbs and uses have an important role in the discovery of new drugs. Nowadays, some of these traditional herbs are researched directly in the clinical trials. In this study, it is aimed to evaluate the 19 plant species that have been identified in the clinical trials among 300 plant species belonging to 79 families with traditional use for skin problems in Turkey. Main body Natural sources are very important to treat diseases for thousands of years. The ethnopharmacological research of natural products ranges from the collection of biogenic samples such as plants to preclinical and clinical studies with the aim of developing drug templates or new drugs. In the ethnopharmacological approach, it is aimed to reach the result based on the traditional and modern knowledge about natural resources. The biggest advantage of this approach is synthesizing new and old information. After the plant or natural compound is determined, other processes work similarly with conventional drugs. Methods Ethnobotanical papers, thesis and projects in Istanbul University Faculty of Pharmacy Department of Pharmaceutical Botany and databases (PubMed and Google Scholar) have been sought and results were synthesized. Results Most of the clinical uses of herbs have been seen similar to their traditional uses. On the other hand, there are some plants on which their clinical uses differ from the traditional uses such as Borago officinalis, Calendula officinalis or Euphorbia peplus. When the frequency of traditional uses of herbs are compared, Plantago species, Plantago major and Plantago lanceolata are the most used taxa in Turkey, secondly, Hypericum perforatum comes. However, Plantago species are not of much interest in clinical trials. It is seen that most of the plants in the clinical research are tried for wound healing occuring due to different origins such as cancer, surgery and injury. Side effects were observed only during the application of Allium cepa, Cydonia oblonga and H. perforatum. Conclusions When clinical trials are evaluated in terms of efficacy and overall results, significant differences and effective results are seen in treatment groups given herbs in comparison with placebo or control groups.


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