Antimycobacterial Activity of Alkaloids and Extracts from Tabernaemontana alba and T. arborea

Planta Medica ◽  
2020 ◽  
Author(s):  
Silvia Laura Guzmán-Gutiérrez ◽  
Mayra Silva-Miranda ◽  
Felix Krengel ◽  
Elizabeth Huerta-Salazar ◽  
Mayra León-Santiago ◽  
...  
Keyword(s):  
Infectious Agent ◽  
Antimycobacterial Activity ◽  
Vero Cells ◽  
World Health ◽  
Root Bark ◽  
Mycobacterium Tuberculosis H37rv ◽  
Resistant Strains ◽  
Alkaloid Extracts ◽  
Health Organization ◽  
Drug Resistant Strains

AbstractTuberculosis is the main cause of death from a single infectious agent. Globally, according to the World Health Organization, in 2018, there were an estimated 1.2 million tuberculosis deaths. Moreover, there is a continuous appearance of drug-resistant strains. Thus, development of new antituberculosis medicines should receive high priority. Plant-derived natural products are promising candidates for this purpose. We therefore screened alkaloid extracts obtained from the root and stem barks of the Mexican Apocynaceae species Tabernaemontana alba and Tabernaemontana arborea, as well as the pure alkaloids ibogaine, voacangine, and voacamine, tested for activity against Mycobacterium tuberculosis H37Rv and cytotoxicity to mammalian Vero cells using the resazurin microtiter and the MTT assays, respectively. The extracts were analyzed by GC-MS and HPLC-UV. T. arborea root bark alkaloid extract showed the highest activity against M. tuberculosis (MIC100 = 7.8 µg/mL) of the four extracts tested. HPLC suggested that voacangine and voacamine were the major components. The latter was isolated by column chromatography, and its chemical structure was elucidated by 1H and 13C NMR, and MS. Unambiguous assignation was performed by HSQC, HMBC, and NOESY experiments. Voacamine is a dimeric bis-indole-type alkaloid and is 15 times more potent than the monomeric ibogan-type alkaloids ibogaine and voacangine (MIC100 = 15.6, 250.0, and 250.0 µg/mL, respectively). However, all of these compounds showed cytotoxicity to Vero cells, with a poor selectivity index of 1.00, 0.16, and 1.42, respectively. This is the first report of voacamine activity against M. tuberculosis.

scholarly journals Tuberculosis drug resistance in Canada, 1998 to 2000

2001 ◽  
Vol 12 (3) ◽  
pp. 141-143
Author(s):  
Melissa D Phypers ◽  
Linda Panaro ◽  
Penny Nault
Keyword(s):  
World Health ◽  
Drug Resistant ◽  
First Line ◽  
International Union ◽  
The World ◽  
Resistant Strains ◽  
Health Organization ◽  
Global Threat ◽  
Drug Resistant Strains ◽  
And Control

The emergence of drug-resistant strains of tuberculosis (TB) is a global threat to TB prevention and control efforts. A recent study conducted by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease found strains of TB resistant to first-line anti-TB drugs in all countries surveyed (1). The WHO estimates that 50 million people are infected with strains of drug-resistant TB (2).

Management of Multidrug-Resistant Tuberculosis

2018 ◽  
Vol 39 (03) ◽  
pp. 310-324 ◽  
Author(s):  
Jose Caminero ◽  
Charles Daley
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Health Organization ◽  
Drug Resistant Strains

AbstractDrug-resistant strains of Mycobacterium tuberculosis pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment of tuberculosis, as well as unchecked transmission of M. tuberculosis, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.

scholarly journals In vitro growth competition experiments that suggest consequences of the substandard artemisinin epidemic that may be accelerating drug resistance in P. falciparum malaria

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248057
Author(s):  
Matthew R. Hassett ◽  
Paul D. Roepe
Keyword(s):  
World Health ◽  
Middle Income ◽  
Middle Income Countries ◽  
Recommended Treatment ◽  
Drug Treatments ◽  
Resistant Strains ◽  
Health Organization ◽  
Treat All ◽  
Drug Resistant Strains

Over the past decade, artemisinin (ART)-combination therapies (ACTs) have shown declining efficacy within Southeast Asia (SEA). These resistance-like phenomena manifest as a delayed clearance phenotype (DCP) in some patients treated with ACTs. ACTs are currently the recommended treatment for P. falciparum infections by the World Health Organization (WHO), and they are our last line of defense to effectively treat all strains of malaria. Acceleration of antimicrobial resistance (AMR) is often theorized to be exacerbated by the use of subtherapeutic dosages of drugs (“substandard” drug), which for ACTs has been well documented over the last decade. Troublingly, in 2017, the WHO estimated that nearly 1 in 10 medical products tested in low- and middle-income countries failed to meet quality standards. We have developed a tissue culture-based approach for testing possible connections between substandard treatment and the spread of ACT resistant blood stage forms of P. falciparum. Via sequencing of pfk13, a molecular marker that is predictive for ART resistance (ARTR), we monitor competition of sensitive vs resistant strains over time and under various conditions and define conditions that favor emergence of ARTR parasites. Our findings help to define the conditions under which substandard drug treatments might favor the proliferation of mutant PfK13-mediated drug resistant strains over drug sensitive.

scholarly journals 5-Alkylamino-N-phenylpyrazine-2-carboxamides: Design, Preparation, and Antimycobacterial Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1561
Author(s):  
Weronika Ambrożkiewicz ◽  
Marta Kučerová-Chlupáčová ◽  
Ondřej Janďourek ◽  
Klára Konečná ◽  
Pavla Paterová ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Importance ◽  
Infectious Agent ◽  
Antimycobacterial Activity ◽  
In Vitro Cytotoxicity ◽  
World Health ◽  
Health Organization ◽  
New Compounds ◽  
Derivatives Of

According to the World Health Organization, tuberculosis is still in the top ten causes of death from a single infectious agent, killing more than 1.7 million people worldwide each year. The rising resistance developed by Mycobacterium tuberculosis against currently used antituberculars is an imperative to develop new compounds with potential antimycobacterial activity. As a part of our continuous research on structural derivatives of the first-line antitubercular pyrazinamide, we have designed, prepared, and assessed the in vitro whole cell growth inhibition activity of forty-two novel 5-alkylamino-N-phenylpyrazine-2-carboxamides with various length of the alkylamino chain (propylamino to octylamino) and various simple substituents on the benzene ring. Final compounds were tested against Mycobacterium tuberculosis H37Ra and four other mycobacterial strains (M. aurum, M. smegmatis, M. kansasii, M. avium) in a modified Microplate Alamar Blue Assay. We identified several candidate molecules with micromolar MIC against M. tuberculosis H37Ra and low in vitro cytotoxicity in HepG2 cell line, for example, N-(4-hydroxyphenyl)-5-(pentylamino)pyrazine-2-carboxamide (3c, MIC = 3.91 µg/mL or 13.02 µM, SI > 38) and 5-(heptylamino)-N-(p-tolyl)pyrazine-2-carboxamide (4e, MIC = 0.78 µg/mL or 2.39 µM, SI > 20). In a complementary screening, we evaluated the in vitro activity against bacterial and fungal strains of clinical importance. We observed no antibacterial activity and sporadic antifungal activity against the Candida genus.

Drug-resistant tuberculosis: World Health Organization launches Global Response Plan 2007-2008

2007 ◽  
Vol 12 (27) ◽  
Author(s):  
Collective Editorial team
Keyword(s):  
World Health ◽  
Drug Resistant ◽  
First Line ◽  
Global Response ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Resistant Strains ◽  
Response Plan ◽  
Health Organization ◽  
Drug Resistant Strains

An increasing proportion of tuberculosis (TB) cases today are resistant to first line, and often also to second line anti-TB drugs. Drug-resistant strains of Mycobacterium tuberculosis are now responsible for over 400,000 cases of TB per year.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis

2010 ◽  
Vol 59 (5) ◽  
pp. 567-572 ◽  
Author(s):  
Fa Ge ◽  
Fanli Zeng ◽  
Siguo Liu ◽  
Na Guo ◽  
Haiqing Ye ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Oleanolic Acid ◽  
Antimycobacterial Activity ◽  
Vero Cells ◽  
Drug Resistant ◽  
Synergistic Interactions ◽  
Combination Treatments ◽  
Low Cytotoxicity ◽  
Drug Resistant Strains

Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50–100 and 100–200 μg ml−1, respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121–0.347, 0.113–0.168 and 0.093–0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.

scholarly journals A framework for the assessment and implementation of diagnostics in outbreak situations

2016 ◽  
Vol 5 (3) ◽  
Author(s):  
Elliot P. Cowan
Keyword(s):  
Infectious Agent ◽  
World Health ◽  
The Us ◽  
Health Need ◽  
Health Organization ◽  
Test Requirements ◽  
Regulatory Evaluation ◽  
Development Assessment ◽  
Outbreak Situation

Observation: Outbreak situations require in vitro diagnostics (IVDs) to identify those who are infected and to track the infectious agent in the population. However, such IVDs are typically not available and must be developed. In addition, the process of IVD development, assessment, and implementation are very time and resource intensive. Recognising the extraordinary public health need for IVDs in an outbreak situation, streamlined processes are needed to provide tests that meet the standard of a reasonable assurance of safety and effectiveness in the shortest amount of time. These IVDs are designated for outbreak use.Addressing Issues: This paper presents a pathway to the outbreak use of IVDs that can be considered by countries experiencing an outbreak situation. It takes into account recognition of the outbreak, product development, regulatory evaluation, implementation, and monitoring of the outbreak-use test. Streamlined assessment programmes for emergency-use tests have been established by the US Food and Drug Administration and the World Health Organization. These programmes take into account test requirements for the country in which the outbreak exists. Therefore, countries can consider adopting these tests without the need to conduct expensive and time consuming assessments, such as performance studies. Key responsible parties are identified for each step of the pathway, recognising that transparency and communication among all parties are critical.

CORONOVIRUS INFECTION COVID-19. MASKS (literature review)

2021 ◽  
Vol 7 (1) ◽  
pp. 24-32
Author(s):  
Semen Kireev ◽  
I. Popov ◽  
A. Ban'kovskiy ◽  
E. Litvinenko ◽  
E. Surova
Keyword(s):  
World Health Organization ◽  
Infectious Agent ◽  
International Committee ◽  
World Health ◽  
Vulnerable Communities ◽  
Regional Director ◽  
The World ◽  
Coronavirus Infection ◽  
Health Organization ◽  
The City

At the end of 2019, an outbreak of a new coronavirus infection occurred in the People's Re-public of China with an epicenter in the city of Wuhan (Hubei province). On February 11, 2020, the World Health Organization has assigned the official name of the infection caused by the new coronavirus - COVID-19 ("Coronavirus disease2019"). On February 11, 2020, the International Committee on Virus Taxonomy gave the official name to the infectious agent - SARS-CoV-2.Since the end of January 2020, cases of COVID-19 have begun to be registered in many coun-tries of the world, mainly associated with travel to the PRC. At the end of February 2020, the epidemiological situation with COVID-19 in South Korea, Iran and Italy sharply worsened, which subsequently led to a significant increase in the number of cases in other countries of the world associated with travel to these countries, incl. and in Russia. The World Health Organiza-tion announced the COVID-19 pandemic on 11 March 2020, and the pandemic's challenge to the world will remain so as long as people are not immune to it.The Regional Director of the World Health Organization Takeshi Kasai, on the basis of an epidemiological analysis, reports that the spread of coronavirus infection COVID-19 in July-August 2020 occurred mainly among people under 50 years old, and they often did not even know about it, because they had mild or no symptoms. In the future, these people then infect older people who are more difficult to tolerate COVID-19. And we need to redouble our efforts to prevent the spread of the virus in vulnerable communities.

scholarly journals Adjuvant Strategies for More Effective Tuberculosis Vaccine Immunity

2019 ◽  
Vol 7 (8) ◽  
pp. 255 ◽  
Author(s):  
Stewart ◽  
Triccas ◽  
Petrovsky
Keyword(s):  
Infectious Agent ◽  
Mechanisms Of Action ◽  
Clinical Development ◽  
World Health ◽  
Effective Vaccine ◽  
Bacillus Calmette Guerin ◽  
Mycobacterium Tuberculosis Infection ◽  
Future Directions ◽  
Vaccine Protection ◽  
Health Organization

Tuberculosis (TB) caused by Mycobacterium tuberculosis infection is responsible for the most deaths by a single infectious agent worldwide, with 1.6 million deaths in 2017 alone. The World Health Organization, through its “End TB” strategy, aims to reduce TB deaths by 95% by 2035. In order to reach this goal, a more effective vaccine than the Bacillus Calmette-Guerin (BCG) vaccine currently in use is needed. Subunit TB vaccines are ideal candidates, because they can be used as booster vaccinations for individuals who have already received BCG and would also be safer for use in immunocompromised individuals in whom BCG is contraindicated. However, subunit TB vaccines will almost certainly require formulation with a potent adjuvant. As the correlates of vaccine protection against TB are currently unclear, there are a variety of adjuvants currently being used in TB vaccines in preclinical and clinical development. This review describes the various adjuvants in use in TB vaccines, their effectiveness, and their proposed mechanisms of action. Notably, adjuvants with less inflammatory and reactogenic profiles that can be administered safely via mucosal routes, may have the biggest impact on future directions in TB vaccine design.

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