ChemInform Abstract: Design and Synthesis of Aryloxyethyl Thiocyanate Derivatives as Potent Inhibitors of Trypanosoma cruzi Proliferation.

SUMMARYNo vaccines or safe chemotherapy are available for Chagas disease. Pentamidine and related di-cations are DNA minor groove-binders with broad-spectrum anti-protozoal activity. Therefore our aim was to evaluate the in vitro efficacy of di-cationic compounds – DB1645, DB1582, DB1651, DB1646, DB1670 and DB1627 – against bloodstream trypomastigotes (BT) and intracellular forms of Trypanosoma cruzi. Cellular targets of these compounds in treated parasites were also analysed by fluorescence and transmission electron microscopy (TEM). DB1645, DB1582 and DB1651 were the most active against BT showing IC50 values ranging between 0·15 and 6·9 μm. All compounds displayed low toxicity towards mammalian cells and DB1645, DB1582 and DB1651 were also the most effective against intracellular parasites, with IC50 values ranging between 7·3 and 13·3 μm. All compounds localized in parasite nuclei and kDNA (with greater intensity in the latter structure), and DB1582 and DB1651 also concentrated in non-DNA-containing cytoplasmic organelles possibly acidocalcisomes. TEM revealed alterations in mitochondria and kinetoplasts, as well as important disorganization of microtubules. Our data provide further information regarding the activity of this class of compounds upon T. cruzi which should aid future design and synthesis of agents that could be used for Chagas disease therapy.

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Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure–activity relationship, toxicity, and mechanism of action

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.105492 ◽

2021 ◽

pp. 105492

Author(s):

Rafael da Rosa ◽

Bibiana Paula Dambrós ◽

Milene Höehr de Moraes ◽

Lucie Grand ◽

Maïwenn Jacolot ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Natural Product ◽

Mechanism Of Action ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Design And Synthesis ◽

Structure Activity

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Design and synthesis of potent substrate-based inhibitors of the Trypanosoma cruzi dihydroorotate dehydrogenase

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2017.01.009 ◽

2017 ◽

Vol 25 (4) ◽

pp. 1465-1470 ◽

Cited By ~ 8

Author(s):

Daniel Ken Inaoka ◽

Maiko Iida ◽

Satoshi Hashimoto ◽

Toshiyuki Tabuchi ◽

Takefumi Kuranaga ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Dihydroorotate Dehydrogenase ◽

Design And Synthesis

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Design and synthesis of novel <em>alfa</em>-mangostin-nitroimidazole hybrids with toxic effects on amastigotes of <em>Trypanosoma cruzi</em>

10.3390/ecmc2020-07434 ◽

2020 ◽

Author(s):

Douglas Pinto ◽

Paulo Santos ◽

Afonso Mesquita-Velez ◽

Gabriella Magalhães ◽

Debora Ricardo ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Toxic Effects ◽

Design And Synthesis

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Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115870 ◽

1975 ◽

Vol 33 ◽

pp. 450-451

Author(s):

W. Allen Shannon ◽

José A. Serrano ◽

Hannah L. Wasserkrug ◽

Anna A. Serrano ◽

Arnold M. Seligman

Keyword(s):

Acid Phosphatase ◽

Phosphate Buffer ◽

Prostatic Carcinoma ◽

Prostatic Acid Phosphatase ◽

Chemotherapeutic Agents ◽

Specific Substrate ◽

Acid Phosphate ◽

Lysosomal Acid ◽

Design And Synthesis ◽

New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

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Tailoring microstructures of materials through biomimetics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100148332 ◽

1993 ◽

Vol 51 ◽

pp. 500-501

Author(s):

Mehmet Sarikaya ◽

Ilhan A. Aksay

Keyword(s):

Chemical Properties ◽

Design And Synthesis ◽

Structure Sensitive ◽

Macro Scale ◽

Methods Of Synthesis ◽

Successive Level ◽

Engineering Materials ◽

Physical And Chemical ◽

And Chemical Properties ◽

Synthesis Of Materials

Biomimetics involves investigation of structure, function, and methods of synthesis of biological composite materials. The goal is to apply this information to the design and synthesis of materials for engineering applications.Properties of engineering materials are structure sensitive through the whole spectrum of dimensions from nanometer to macro scale. The goal in designing and processing of technological materials, therefore, is to control microstructural evolution at each of these dimensions so as to achieve predictable physical and chemical properties. Control at each successive level of dimension, however, is a major challenge as is the retention of integrity between successive levels. Engineering materials are rarely fabricated to achieve more than a few of the desired properties and the synthesis techniques usually involve high temperature or low pressure conditions that are energy inefficient and environmentally damaging.In contrast to human-made materials, organisms synthesize composites whose intricate structures are more controlled at each scale and hierarchical order.

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