A5048642508- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Click Chemistry and Applications
- Quinazolinone synthesis and applications
- Traditional and Medicinal Uses of Annonaceae
- Lysosomal Storage Disorders Research
- Toxin Mechanisms and Immunotoxins
- Cancer Treatment and Pharmacology
- Phenothiazines and Benzothiazines Synthesis and Activities
- Berberine and alkaloids research
- Insect and Pesticide Research
- Microtubule and mitosis dynamics
- Parasitic Infections and Diagnostics
- Synthesis of heterocyclic compounds
- Malaria Research and Control
- Toxoplasma gondii Research Studies
- Phytochemistry and biological activities of Ficus species
- HIV/AIDS drug development and treatment
- Fungal Plant Pathogen Control
- Weed Control and Herbicide Applications
- Carbohydrate Chemistry and Synthesis
The Ohio State University
2013-2024
Andhra University
2022
American Association of Colleges of Pharmacy
2013-2014
University of Dundee
2010
Wellcome Trust
2010
University of California, Irvine
2010
Swiss Tropical and Public Health Institute
2004-2009
University of North Carolina at Chapel Hill
2008
Georgia State University
2003-2007
Walter Reed Army Institute of Research
1998-2006
Novel dicationic triazoles 1−60 were synthesized by the Pinner method from corresponding dinitriles, prepared via copper(I)-catalyzed azide−alkyne cycloaddition (CuAAC). The type and placement of cationic moieties as well nature aromatic substituents influenced in vitro antiprotozoal activities compounds against Trypanosoma brucei rhodesiense, Plasmodium falciparum, Leishmania donovani their cytotoxicity for mammalian cells. Eight congeners displayed antitrypanosomal IC50 values below 10 nM....
A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against Leishmania donovani L. amazonensis intracellular amastigotes. structure-activity structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This led identification quinazolines with EC50 values single digit micromolar or high nanomolar range addition favorable physicochemical properties. Quinazoline 23 also displayed...
Visceral leishmaniasis is a deadly parasitic disease caused by obligate intramacrophage protozoans of the Leishmania genus. The World Health Organization estimates annual death toll to be 50,000, with 500,000 new cases each year. Without treatment, visceral inevitably fatal. For last 70 years, first line defense has been pentavalent antimonials; however, increased resistance brought amphotericin B forefront treatment options. Unfortunately, difficult route drug administration, toxicity...
Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC(50)], <1 microM) against both Leishmania donovani axenic amastigotes and intracellular Leishmania, the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize in vitro vivo activities, pharmacokinetics, mutagenicities, toxicities two novel AIAs, DB745 DB766. They were exceptionally active...
The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent vivo activity. While 6-ether derivatives were less active than compound, several N1-substituted displayed nanomolar IC50 values against T. b. rhodesiense STIB900 vitro, selectivity...
Forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with α-halogenated ketones followed intramolecular ring closure or a copper- palladium-mediated heteroannulation substituted o-iodophenols terminal acetylenes. In vitro antiprotozoal activities compounds 1−43 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani cytotoxicity mammalian cells influenced the position type substituents as well length carbon linker...
Purpose To develop an oral formulation of amphotericin B (AmB) that is stable at the temperatures WHO Climatic Zones 3 and 4 (30–43°C) to evaluate its efficacy in a murine model visceral leishmaniasis (VL). Methods The stability testing four novel lipid AmB formulations composed mono- di-glycerides pegylated esters (iCo-010 iCo-013) was performed over 60 d analyzed by HPLC-UV. In addition, were incubated h fasted-state simulated intestinal fluid. concentration measured spectrophotometrically...
Diamidine 1 (pentamidine) and 65 analogues (2−66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, Leishmania donovani, cytotoxicity mammalian cells. Dications 32, 64, 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC50 = 4 nM). Nine congeners (2−4, 12, 27, 30, 64−66) were more active P. falciparum artemisinin 6 Eight compounds (12, 33, 44, 59, 62, 66) better antileishmanial 1.8 μM). Several...
Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and 7,8-seco-abietane (2), 14 other known highly oxidized diterpenoids (3–16) were isolated from an extract prepared the cones of Taxodium distichum, collected in central Ohio. The active subfraction which all compounds this study purified was tested vivo using Leishmania donovani-infected mice found to dose-dependently reduce parasite burden murine livers after iv administration crude mixture at 5.6 11.1 mg/kg....
ABSTRACT Aromatic dicationic molecules possess impressive activity against a broad spectrum of microbial pathogens, including Pneumocystis carinii , Cryptosporidium parvum and Candida albicans . In this work, 58 aromatic cations were examined for inhibitory axenic amastigote-like Leishmania donovani parasites. general, the most potent compounds substituted diphenyl furan thiophene dications. 2,5-Bis-(4-amidinophenyl)thiophene was active compound. This agent displayed 50% concentration (IC 50...
Analogs of the antimitotic herbicide oryzalin (3,5-dinitro-<i>N</i>4,<i>N</i>4-di-<i>n</i>-propylsulfanilamide) were recently prepared that more potent in vitro than parent compound against kinetoplastid parasite <i>Leishmania donovani</i> (<i>Bioorg Med Chem Lett</i><b>12:</b>2395-2398, 2002). In present work, we show most active molecule group, <i>N</i>1-phenyl-3,5-dinitro-<i>N</i>4,<i>N</i>4-di-<i>n</i>-propylsulfanilamide (GB-II-5), is a potent, selective agent parasites. GB-II-5...
Bioactivity-guided fractionation of the methanolic extract Psorothamnus polydenius yielded new chalcone 2,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), together with six other known compounds, 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (1), dalrubone (3), demethoxymatteucinol (4), eriodictyol (5), and photodalrubone (6a 6b). This is first report chalcones in P. polydenius. The extracts isolated compounds were tested vitro for their antiprotozoal activity against Leishmania...
ABSTRACT Plant and protozoan microtubules are selectively sensitive to dinitroanilines, which do not disrupt vertebrate or fungal microtubules. Tetrahymena thermophila is an abundant source of dinitroaniline-sensitive tubulin, we have modified the single T. α-tubulin gene create strains that solely express mutant in functional dimers. Previous research identified multiple mutations confer dinitroaniline resistance human parasite Toxoplasma gondii , when two these (L136F I252L) were...
4,4″-Diamidino-m-terphenyl (1) and 36 analogues were prepared assayed in vitro against Trypanosoma brucei rhodesiense, cruzi, Plasmodium falciparum, Leishmania amazonensis. Twenty-three compounds highly active T. b. rhodesiense or P. falciparum. Most noteworthy amidines 1, 10, 11 with IC50 of 4 nM dimethyltetrahydropyrimidinyl 9 values ≤ 3 Bis-pyridylimidamide derivative 31 was 25 times more potent than benznidazole cruzi slightly amphotericin B L. Terphenyldiamidine 1 dipyridylbenzene 23...
Human leishmaniasis is an infectious disease caused by Leishmania protozoan parasites. Current chemotherapeutic options against the deadly have significant limitations. The ergosterol biosynthetic pathway has been identified as a drug target in Leishmania. However, remarkable differences efficacy of antifungal azoles that inhibit biosynthesis reported for treatment leishmaniasis. To better understand sterol and elucidate mechanism underlying differential azoles, we developed new LC-MS/MS...