Leishmaniasis treatment—a challenge that remains: a review (original) (raw)
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Applied Life Science Synthetic and Natural Products Against Leishmaniasis: A Review
2012
Leishmaniasis, a group of tro pical diseases resulting from infection of macrophages by obligate intracellular parasites of genus Leishmania, is a major health problem worldwide. The World Health Organization has classified the leishmaniasis as a major tropical disease. Growing incidence of resistance for the generic pentavalent antimony complex for treatment in endemic and non-endemic regions has seriously hampered their use. The second line drugs such as amphotericin B, paromomycin and miltefosine are the other alternatives, but they merely fulfill the requirements of a safe drug. The recent researches focused on some synthetic agents like chalcones and natural products have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis. The aim of this article is to review the current aspects of the pharmacology of leishmaniasis, giving an overview from current agents clinically used to new compounds under development. The current scenario of ...
2021
Despite advancements in the areas of omics and chemoinformatics, potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis. The socioeconomic burden of leishmaniasis remains alarming in endemic regions. Currently, reports from existing endemic areas such as Nepal, Iran, Brazil, India, Sudan and Afghanistan, as well as newly affected countries such as Peru, Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial treatment. As a result, effective antileishmanial agents which are safe and affordable are urgently needed. Natural products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical agents. This review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last decade. Furthermore, IC50/EC50, cytotoxicity and suggested mechanisms of action of some of these natural products are provided. ...
Therapeutic Arsenal against Leishmaniases: A Review
International Journal of TROPICAL DISEASE & Health, 2015
Leishmaniases are included in the group of reemerging neglected tropical diseases caused by flagellated parasites of the Leishmania genus. WHO recommends the use of chemotherapy as the main control measure for all the types of the disease. Antimonials are the first drug of choice, but they can be replaced by amphotericin B, mitelfosine, paromomycin and pentamidine isethionate, or combinations. Generally, all the medicines that contain these drugs have several drawbacks. In view of this, chemotherapy for Leishmaniasis is increasingly the object of study, searching for safer or more effective drugs or new drug delivery vehicles, where nanotechnology is crucial. Thus, the purpose of this review is to present the therapeutic arsenal available in the market and that has been investigated for this application. IJTDH, 5(2): 101-122, 2015; Article no.IJTDH.2015.011 102
Natural product based leads to fight against leishmaniasis
Bioorganic & Medicinal Chemistry, 2014
The growing incidence of parasitic resistance against generic pentavalent antimonials, specifically for visceral disease in Indian subcontinent, is a serious issue in Leishmania control. Notwithstanding the two treatment alternatives, that is amphotericin B and miltefosine are being effectively used but their high cost and therapeutic complications limit their use in endemic areas. In the absence of a vaccine candidate, identification, and characterization of novel drugs and targets is a major requirement of leishmanial research. This review describes current drug regimens, putative drug targets, numerous natural products that have shown promising antileishmanial activity alongwith some key issues and strategies for future research to control leishmaniasis worldwide.
Chemotherapy of Leishmaniasis: Past, Present and Future
Current Medicinal Chemistry, 2007
Leishmaniasis is a parasitic disease caused by hemoflagellate, Leishmania spp. The parasite is transmitted through the bites of an infected female phlebotomine sandfly. Leishmaniasis is prevalent throughout the world and in at least 88 countries. For its treatment, nearly 25 compounds are reported to have anti-leishmanial effects but not all are in use. Pentavalent antimony compounds had remained mainstay for nearly 75 years. However, emergence of resistance to this drug, led to the use of other compounds such as -Amphotericin B, Pentamidine, Paromomycin, Allopurinol etc. Amphotericin B, an antifungal macrolide polyene is characterized by the hydrophilic polyhydroxyl and hydrophobic polyene faces on it long axis which acts on membrane sterols resulting in parasite cell lysis. Presently, it is the only drug with highest cure rate. Other anti-fungals like ketoconazole, fluconazole and terbinafine are found less effective. Recently, anticancer alkylphosphocholines have been found to be the most effective oral compounds. These act as membrane synthetic ether-lipid analogues, and consist of alkyl chains in the lipid portions. Most promising of these are miltefosine (hexadecylphosphocholine), Edelfosine (ET-18-OCH 3 ) and Ilmofosine (BM 41.440). However, the recent focus has been on identifying newer therapeutic targets in the parasite such as DNA topoisomerases. The present review describes the current understanding of different drugs against leishmaniasis, their chemistry, mode of action and the mechanism of resistance in the parasite. Future perspectives in the area of new anti-leishmanial drug targets are also enumerated. However, due to the vastness of the topic main emphasis is given on visceral leishmaniasis.
Rational Approaches for Drug Designing Against Leishmaniasis
Applied Biochemistry and Biotechnology, 2010
Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.
Leishmaniasis: An appraisal of current medications and potential natural sources
2013
Leishmaniasis is found in every continent except Au stralia and Antarctica. Among all 90% of VL cases have been found in Bangladesh, Brazil, India, Nepal and Sudan , where as CL was found more common in Afghanistan, Brazil, Iran, Peru, Saudi Arabia, Syria and the least commo n MCL was found prevalent in Bolivia, Brazil and P eru. Each year, approximately 0.7-1.2 million people sufferin g from CL and 0.2-0.4 million people suffering from VL. The resistance of leishmania parasites to antimonial dr ugs, especially pentavalent antimonials is one of t he main causes for rapid spread and exponential rise in number of cases which makes the situation more critical. With increasing international travel, leishmaniasis is being import ed into those areas where it was not previously see n and opportunistic infections are now being reported (pa rticularly in AIDS patients) [5]. Life cycle of leishmania parasite
Alternative to Chemotherapy-The Unmet Demand against Leishmaniasis
Frontiers in immunology, 2017
Leishmaniasis is a neglected protozoan disease that mainly affects the tropical as well as subtropical countries of the world. The primary option to control the disease still relies on chemotherapy. However, a hindrance to treatments owing to the emergence of drug-resistant parasites, enormous side effects of the drugs, their high cost, and requirement of long course hospitalization has added to the existing problems of leishmaniasis containment program. This review highlights the prospects of immunotherapy and/or immunochemotherapy to address the limitations for current treatment measures for leishmaniasis. In addition to the progress in alternate therapeutic strategies, the possibility and advances in developing preventive measures against the disease have been pointed. The review highlights our recent understandings of the protective immunology that can be exploited to develop an effective vaccine against leishmaniasis. Moreover, an update on the approaches that have evolved over...
Exploration of Antileishmanial Compounds Derived from Natural Sources
Leishmaniasis is considered one of the different neglected tropical diseases by the World Health Organization. Over the past few decades to tackle leishmaniasis, effective and novel drugs have progressed. But few are expensive some other medication shows poor effects and few drugs with long treatment lead to cause resistance. But it is very important to start a better medication against leishmania so researchers came to the front of the utilization of natural products which are considered a better option. Finding active compounds in medicinal plants is another alternative to currently accessible medications. Materials and methods: This study examined and reported the far more potential natural products used to treat disease caused by Leishmania spp. Leishmaniasis, plant metabolites, in vivo, in vitro, and treatment against leishmaniasis have been used as search terms in the Google Scholar, PubMed, and Science Direct databases, and only papers published between 2015 and 2021 have bee...
SEARCH FOR NEW ANTILEISHMANIAL CHEMOTHERAPEUTICS Original Article
International Journal of Pharmacy and Pharmaceutical Sciences, 2018
Objective: The objective of this work was to screen a number of compounds for their antileishmanial efficacy and cytotoxicity profiling. Methods: Curry leaf oil, cypress oil and spikenard oil were identified by gas chromatography-mass spectrometry (GC/MS) analysis. Betulinic acid, spikenard oil, cypress oil and curry leaf oil were evaluated for their in vitro antileishmanial activity against Leishmania donovani AG83 wild-type, sodium stibogluconate resistant (SSG-resistant), paromomycin (PMM-resistant) and GE1 field type strains on axenic and cellular amastigote model and compared the results with standard drugs used to treat leishmaniasis. Results: Betulinic acid showed strong antileishmanial activity against wild-type (SI= 192.8), SSG-resistant (SI= 19.3) and GE1 strains (SI= 100), whereas cypress oil has produced highest antileishmanial activity against PMM-resistant strains (SI= 15.09) among all the tested drugs. The data obtained also revealed that cypress oil had the maximum CC50 Conclusion: All tested drugs had antileishmanial property but among them, betulinic acid possess strong antileishmanial activity in case of both wild-type and drug-resistant leishmaniasis. value of 452.9 μl among all standard and tested drugs.