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Article ; Online: Corrigendum to "Biofunctionalized chrysin-conjugated gold nanoparticles neutralize Leishmania parasites with high efficacy" [Int. J. Biol. Macromol. Volume 205, 30 April 2022, Pages 211-219].

Raj, Shweta / Sasidharan, Santanu / Tripathi, Timir / Saudagar, Prakash

International journal of biological macromolecules

2024 Volume 264, Issue Pt 2, Page(s) 130924

Language	English
Publishing date	2024-03-19
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.130924
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Article ; Online: Geospatial Health (GeoHealth): Current Trends, Methods, and Applications.

Osei, Frank Badu / Sasidharan, Santanu

Tropical medicine and infectious disease

2023 Volume 8, Issue 7

Abstract: As an emerging field, Geospatial Health (GeoHealth) integrates geospatial technologies, (spatial) epidemiology, and health services/resource allocations (health accessibility), with a focus to fight the burden of diseases [ ... ]. ...

Abstract	As an emerging field, Geospatial Health (GeoHealth) integrates geospatial technologies, (spatial) epidemiology, and health services/resource allocations (health accessibility), with a focus to fight the burden of diseases [...].
Language	English
Publishing date	2023-07-17
Publishing country	Switzerland
Document type	Editorial
ISSN	2414-6366
ISSN (online)	2414-6366
DOI	10.3390/tropicalmed8070366
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Article ; Online: An anti-leishmanial compound 4',7-dihydroxyflavone elicits ROS-mediated apoptosis-like death in Leishmania parasite.

Sasidharan, Santanu / Saudagar, Prakash

The FEBS journal

2023 Volume 290, Issue 14, Page(s) 3646–3663

Abstract: The treatment for leishmaniasis is currently plagued by side effects such as toxicity and the emergence of drug resistance to the available repertoire of drugs, as well as the expense of these drugs. Considering such rising concerns, we report the anti- ... ...

Abstract	The treatment for leishmaniasis is currently plagued by side effects such as toxicity and the emergence of drug resistance to the available repertoire of drugs, as well as the expense of these drugs. Considering such rising concerns, we report the anti-leishmanial activity and mechanism of a flavone compound 4',7-dihydroxyflavone (TI 4). Four flavanoids were initially screened for anti-leishmanial activity and cytotoxicity. The results showed that the compound TI 4 exhibited higher activity and selectivity index at the same time as maintaining low cytotoxicity. Preliminary microscopic studies and fluorescence-activated cell sorting analysis reported that the parasite underwent apoptosis on TI 4 treatment. Further in-depth studies revealed high reactive oxygen species (ROS) production and thiol levels in the parasites, suggesting ROS-mediated apoptosis in the parasites upon TI 4 treatment. Other apoptotic indicators such as intracellular Ca
MeSH term(s)	Animals ; Leishmania/metabolism ; Parasites/metabolism ; Reactive Oxygen Species/metabolism ; Leishmaniasis/drug therapy ; Apoptosis ; Antiprotozoal Agents/pharmacology
Chemical Substances	4',7-dihydroxyflavone (53ZZF57X0U) ; Reactive Oxygen Species ; Antiprotozoal Agents
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16770
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Article ; Online: 4',7-dihydroxyflavone conjugated carbon nanotube formulation demonstrates improved efficacy against Leishmania parasite.

Sasidharan, Santanu / Saudagar, Prakash

Biochimica et biophysica acta. General subjects

2023 Volume 1867, Issue 10, Page(s) 130416

Abstract: One of the global problems of rising concern is the spread of the neglected tropical disease, leishmaniasis. There are several drugs used for the treatment of the disease but the repertoire of drugs has drawbacks like toxicity and low therapeutic value. ... ...

Abstract	One of the global problems of rising concern is the spread of the neglected tropical disease, leishmaniasis. There are several drugs used for the treatment of the disease but the repertoire of drugs has drawbacks like toxicity and low therapeutic value. Considering the need for new drugs, we studied the synthesis of 4',7-dihydroxyflavone conjugated multi-walled carbon nanotubes (47DHF-MWCNTs) and evaluated their anti-leishmanial activity against Leishmania donovani. The compound 47DHF was conjugated to the acid oxidized MWCTNs by Steglich esterification. The synthesized 47DHF-MWCNTs were characterized by UV spectroscopy, and, from the zeta value of 35 mV, they were found to be stable. 47DHF-MWCNTs possessed 84% drug loading efficiency and 63% cumulative drug release at intra-macrophage pH of 5.8. Moreover, the evaluation of 47DHF-MWCNTs for activity showed an IC
MeSH term(s)	Animals ; Nanotubes, Carbon ; Parasites ; Reactive Oxygen Species ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/chemistry ; Leishmania donovani ; Leishmaniasis/drug therapy
Chemical Substances	Nanotubes, Carbon ; Reactive Oxygen Species ; 4',7-dihydroxyflavone (53ZZF57X0U) ; Antiprotozoal Agents
Language	English
Publishing date	2023-07-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2023.130416
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Article ; Online: An anti‐leishmanial compound 4′,7‐dihydroxyflavone elicits ROS‐mediated apoptosis‐like death in Leishmania parasite

Sasidharan, Santanu / Saudagar, Prakash

The FEBS Journal. 2023 July, v. 290, no. 14 p.3646-3663

2023

Abstract	The treatment for leishmaniasis is currently plagued by side effects such as toxicity and the emergence of drug resistance to the available repertoire of drugs, as well as the expense of these drugs. Considering such rising concerns, we report the anti‐leishmanial activity and mechanism of a flavone compound 4′,7‐dihydroxyflavone (TI 4). Four flavanoids were initially screened for anti‐leishmanial activity and cytotoxicity. The results showed that the compound TI 4 exhibited higher activity and selectivity index at the same time as maintaining low cytotoxicity. Preliminary microscopic studies and fluorescence‐activated cell sorting analysis reported that the parasite underwent apoptosis on TI 4 treatment. Further in‐depth studies revealed high reactive oxygen species (ROS) production and thiol levels in the parasites, suggesting ROS‐mediated apoptosis in the parasites upon TI 4 treatment. Other apoptotic indicators such as intracellular Ca²⁺ and mitochondrial membrane potential also indicated the onset of apoptosis in the treated parasites. The mRNA expression levels signified that the redox metabolism genes were upregulated by two‐fold along with the apoptotic genes. In summary, the use of TI 4 on Leishmania parasites induces ROS‐mediated apoptosis; therefore, the compound has immense potential to be an anti‐leishmanial drug. However, in vivo studies would be required to ascertain its safety and efficacy before we can exploit the compound against the growing leishmaniasis crisis.
Keywords	Leishmania ; antileishmanial properties ; antileishmanials ; apoptosis ; calcium ; cytotoxicity ; death ; drug resistance ; flavanoids ; flavones ; gene expression ; leishmaniasis ; membrane potential ; metabolism ; mitochondrial membrane ; parasites ; reactive oxygen species ; thiols
Language	English
Dates of publication	2023-07
Size	p. 3646-3663.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16770
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Article ; Online: Knockout of Tyrosine Aminotransferase Gene by Homologous Recombination Arrests Growth and Disrupts Redox Homeostasis in Leishmania Parasite.

Sasidharan, Santanu / Saudagar, Prakash

Parasitology research

2022 Volume 121, Issue 11, Page(s) 3229–3241

Abstract: Tyrosine aminotransferase is a well-characterized enzyme in the Leishmania parasite, but the role of TAT in the parasite functioning remains largely unknown. In this study, we attempt to gain a better understanding of the enzyme's role in the parasite by ...

Abstract	Tyrosine aminotransferase is a well-characterized enzyme in the Leishmania parasite, but the role of TAT in the parasite functioning remains largely unknown. In this study, we attempt to gain a better understanding of the enzyme's role in the parasite by gene knockout and overexpression of the TAT gene. The overexpression of TAT protein was well tolerated by the parasites in two independent repeats. Single knockout of TAT gene by homologous recombination, LdTAT
MeSH term(s)	Animals ; Gene Products, tat/genetics ; Gene Products, tat/metabolism ; Homeostasis ; Homologous Recombination ; Leishmania donovani ; Oxidation-Reduction ; Parasites/metabolism ; Reactive Oxygen Species/metabolism ; Sulfhydryl Compounds/metabolism ; Tocopherols/metabolism ; Tyrosine Transaminase/chemistry ; Tyrosine Transaminase/genetics ; Tyrosine Transaminase/metabolism
Chemical Substances	Gene Products, tat ; Reactive Oxygen Species ; Sulfhydryl Compounds ; Tyrosine Transaminase (EC 2.6.1.5) ; Tocopherols (R0ZB2556P8)
Language	English
Publishing date	2022-09-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-022-07642-0
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Article ; Online: Gold and silver nanoparticles functionalized with 4',7-dihydroxyflavone exhibit activity against Leishmania donovani.

Sasidharan, Santanu / Saudagar, Prakash

Acta tropica

2022 Volume 231, Page(s) 106448

Abstract: Leishmaniasis is a neglected tropical disease that has been burdening the world for over a century. Though there are drugs to treat leishmaniasis, the repertoire suffers several drawbacks like toxicity and low therapeutic value. Therefore, there is a ... ...

Abstract	Leishmaniasis is a neglected tropical disease that has been burdening the world for over a century. Though there are drugs to treat leishmaniasis, the repertoire suffers several drawbacks like toxicity and low therapeutic value. Therefore, there is a rising concern to develop new anti-leishmanial strategies. In this study, we report, for the first time, the one-pot synthesis method and functionalization of gold and silver nanoparticles with 4',7-dihydroxyflavone (Au-47DHF and Ag-47DHF)) and their anti-leishmanial activity. Oval and spherical-shaped Au-47DHF nanoparticles were obtained with an average size of 5.8 ± 0.1 nm and while synthesized dodecahedron-shaped Ag-47DHF had an average size of 25.1 ± 1 nm. The zeta potential of Au-47DHF and Ag-47DHF were measured to be stable with values of 40 mV and 60 mV, respectively. The functionalization of nanoparticles with 4',7-dihydroxyflavone was confirmed by FTIR spectra. Both Au-47DHF and Ag-47DHF exhibited promising anti-leishmanial activity against the promastigote forms with IC
MeSH term(s)	Flavonoids ; Gold/pharmacology ; Leishmania donovani ; Metal Nanoparticles ; Reactive Oxygen Species ; Silver/pharmacology
Chemical Substances	Flavonoids ; Reactive Oxygen Species ; Silver (3M4G523W1G) ; 4',7-dihydroxyflavone (53ZZF57X0U) ; Gold (7440-57-5)
Language	English
Publishing date	2022-04-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	210415-5
ISSN	1873-6254 ; 0001-706X
ISSN (online)	1873-6254
ISSN	0001-706X
DOI	10.1016/j.actatropica.2022.106448
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Article ; Online: Knockout of Tyrosine Aminotransferase Gene by Homologous Recombination Arrests Growth and Disrupts Redox Homeostasis in Leishmania Parasite

Sasidharan, Santanu / Saudagar, Prakash

Parasitol Res. 2022 Nov., v. 121, no. 11 p.3229-3241

2022

Abstract	Tyrosine aminotransferase is a well-characterized enzyme in the Leishmania parasite, but the role of TAT in the parasite functioning remains largely unknown. In this study, we attempt to gain a better understanding of the enzyme’s role in the parasite by gene knockout and overexpression of the TAT gene. The overexpression of TAT protein was well tolerated by the parasites in two independent repeats. Single knockout of TAT gene by homologous recombination, LdTAT⁺/⁻ displayed distinct retardation in the proliferation rates and entered the death phase immediately. Morphology of LdTAT⁺/⁻ parasites had important structural defects as they rounded up with elongated flagella. Gene regulation studies suggested the upregulation of key apoptotic and redox metabolism genes in LdTAT⁺/⁻. Moreover, LdTAT⁺/⁻ cells accumulated higher ROS, thiols, intracellular Ca²⁺ concentrations, and mitochondrial membrane depolarization signifying the onset of apoptosis. Tocopherol levels were reduced by 50% in LdTAT⁺/⁻ suggesting the involvement of TAT in tocopherol biosynthesis in the parasite. Overall, our results provide the first evidence that gene knockout of TAT results in apoptosis and that TAT is required for the survival and viability of Leishmania donovani.
Keywords	Leishmania donovani ; apoptosis ; biosynthesis ; calcium ; death ; flagellum ; gene targeting ; genes ; homeostasis ; homologous recombination ; mitochondrial membrane ; parasites ; thiols ; tyrosine transaminase ; viability
Language	English
Dates of publication	2022-11
Size	p. 3229-3241.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-022-07642-0
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Article: Gold and silver nanoparticles functionalized with 4’,7-dihydroxyflavone exhibit activity against Leishmania donovani

Sasidharan, Santanu / Saudagar, Prakash

Acta tropica. 2022 July, v. 231

2022

Abstract	Leishmaniasis is a neglected tropical disease that has been burdening the world for over a century. Though there are drugs to treat leishmaniasis, the repertoire suffers several drawbacks like toxicity and low therapeutic value. Therefore, there is a rising concern to develop new anti-leishmanial strategies. In this study, we report, for the first time, the one-pot synthesis method and functionalization of gold and silver nanoparticles with 4’,7-dihydroxyflavone (Au-47DHF and Ag-47DHF)) and their anti-leishmanial activity. Oval and spherical-shaped Au-47DHF nanoparticles were obtained with an average size of 5.8 ± 0.1 nm and while synthesized dodecahedron-shaped Ag-47DHF had an average size of 25.1 ± 1 nm. The zeta potential of Au-47DHF and Ag-47DHF were measured to be stable with values of 40 mV and 60 mV, respectively. The functionalization of nanoparticles with 4’,7-dihydroxyflavone was confirmed by FTIR spectra. Both Au-47DHF and Ag-47DHF exhibited promising anti-leishmanial activity against the promastigote forms with IC₅₀ values of 0.1226 ± 0.02 µg/ml and 0.8483 ± 0.14 µg/ml, respectively. The nanoparticles were also capable of anti-intracellular amastigote activity with 0.121 ± 0.36 µg/ml and 0.215 ± 0.85 µg/ml for Au-47DHF and Ag-47DHF, respectively. Interestingly, the treatment with Au-47DHF and Ag-47DHF nanoparticles generated high ROS concentrations in the parasites suggesting a ROS-mediated anti-leishmanial activity of Au-47DHF and Ag-47DHF. Concluding from the results, we present here a novel synthesis method of Au-47DHF and Ag-47DHF nanoparticles that have immense potential to be anti-leishmanial agents.
Keywords	Leishmania donovani ; antileishmanial properties ; gold ; leishmaniasis ; nanosilver ; synthesis ; therapeutics ; toxicity ; tropical diseases ; zeta potential
Language	English
Dates of publication	2022-07
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	210415-5
ISSN	1873-6254 ; 0001-706X
ISSN (online)	1873-6254
ISSN	0001-706X
DOI	10.1016/j.actatropica.2022.106448
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Article ; Online: Leishmaniasis: where are we and where are we heading?

Sasidharan, Santanu / Saudagar, Prakash

Parasitology research

2021 Volume 120, Issue 5, Page(s) 1541–1554

Abstract: Leishmaniasis is a zoonotic disease in humans caused by the bite of a parasite-infected sandfly. The disease, widely referred to as "poor man's disease," affects millions of people worldwide. The clinical manifestation of the disease depends upon the ... ...

Abstract	Leishmaniasis is a zoonotic disease in humans caused by the bite of a parasite-infected sandfly. The disease, widely referred to as "poor man's disease," affects millions of people worldwide. The clinical manifestation of the disease depends upon the species of the parasite and ranges from physical disfigurement to death if left untreated. Here, we review the past, present, and future of leishmaniasis in detail. The life cycle of Leishmania sp., along with its epidemiology, is discussed, and in addition, the line of therapeutics available for treatment currently is examined. The current status of the disease is critically evaluated, keeping emerging threats like human immunodeficiency virus (HIV) coinfection and post kala-azar dermal leishmaniasis (PKDL) into consideration. In summary, the review proposes a dire need for new therapeutics and reassessment of the measures and policies concerning emerging threats. New strategies are essential to achieve the goal of leishmaniasis eradication in the next few decades.
MeSH term(s)	Animals ; Coinfection/pathology ; Female ; HIV Infections/pathology ; Humans ; Leishmania donovani/pathogenicity ; Leishmaniasis, Cutaneous/epidemiology ; Leishmaniasis, Cutaneous/pathology ; Leishmaniasis, Visceral/epidemiology ; Leishmaniasis, Visceral/pathology ; Male ; Psychodidae/parasitology ; Zoonoses/pathology
Language	English
Publishing date	2021-04-07
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-021-07139-2
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