Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Kubohara, Yuzuru; Kikuchi, Haruhisa

doi:10.3390/cells8010006

Cited by 23 publications

(33 citation statements)

References 114 publications

(215 reference statements)

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“…On the other hand, Pf-2 was found to lack any substantial cytotoxicity.Pf-1 and AB0022A exhibited the constraint of the tested cell lines (K562, HeLa and 3T3-L1), which indicates that a free phenolic group connected to carbonyl is necessary for activity. Despite the lack of IC 50 values reports, AB0022A proved effectual against the three cell lines compared to Pf-1 [44] (Fig. 2).…”

Section: All the Polychlorinated Biphenyl (Pcb) Andmentioning

confidence: 90%

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Synthesis of Dibenzofuran Derivatives Possessing Anticancer Activities: A Review

Moustafa¹,

Al-Wasidi

Naglah

et al. 2020

Egypt. J. Chem.

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Synthesis of Dibenzofuran Derivatives Pschorr Reaction The preparation of biaryltricyclics rings is facilitated by the Pschorr Reaction via intramolecular means by substituting one arene by the aryl radical. The said radical is created in situ from the aryl diazonium salt by a copper catalysis. Despite the use of excess copper salts, the yield is optimally moderate. Two more soluble alternative electron donors have been f (refer to Modern Literature). The method in the current report improves output at a shorter reaction time (scheme 1). Recent Methods Catalysis of palladium provides an intracellular cycle for ethyl diazonium salts of diaryl ether to produce dibenzofurans. This process uses 3% molpalladium acetate as an aid in refluxing ethanol without a base (scheme 2) [1]. Intramolecular palladium (II) catalyzes the formation of carbon-and oxidized carbon bonds under air in the presence of pivalic acid where in the reaction's solvent, rather than the acetic acid, leads to more reproduction and productivity and wider substrate range. The reaction allows the conversion of both electron-rich electron amines and electron deficiency (scheme 3) [2]. T HIS review focuses on reports concerning the isolation and/or synthesis of dibenzofuran derivatives' isolation and synthesis (whether one of them or both occurs simultaneously) existing naturally while exhibiting evident biological anticancer activity. While not a comprehensive approach to all relevant compounds, the review intends to demonstrate anticancer activity's reach related to said compounds instead and the various natural origins and synthetic methods from which and by which the compounds are to be secluded and prepared. Compounds with reduced benzene rings, e.g., morphine as well as its derivatives, are omitted, same for compounds with aromaticity disrupted by alkylation, as with usnic acid.

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Section: All the Polychlorinated Biphenyl (Pcb) Andmentioning

confidence: 90%

“…1). Two dibenzofurans dubbed Pf-1 and Pf-2 were recently secluded from dictyostelium discoideum, another slime mold [43,44].…”

Section: All the Polychlorinated Biphenyl (Pcb) Andmentioning

confidence: 99%

Synthesis of Dibenzofuran Derivatives Possessing Anticancer Activities: A Review

Moustafa¹,

Al-Wasidi

Naglah

et al. 2020

Egypt. J. Chem.

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“…These studies have now been extended to the characterization of curcumin and naringenin, which were found to inhibit development and/or growth (Cocorocchio et al, 2018;Swatson et al, 2017;Garige and Walters, 2015;Waheed et al, 2014). The polyketide Differentiation Inducing Factors (DIFs) 1-3, which are produced by Dictyostelium cells and induce stalk cell differentiation (Masento et al, 1988), and several of their synthetic derivatives have been shown to have not only anti-tumoral (Arioka et al, 2017;Dubois et al, 2016;Kubokura et al, 2015;Takahashi-Yanaga et al, 2014), but also anti-microbial activities, interestingly against Gram-positive, but not Gram-negative, bacteria (Kubohara et al, 2019), suggesting that Dictyostelium can be an important source in drug discovery (Kubohara and Kikuchi, 2018).…”

Section: Dictyostelium As a Model For Biomedical Research: Recent Conmentioning

confidence: 99%

“…There are, clearly, some limitations that make studies with lower organisms still unavoidable (Rine, 2014). Human disease phenotypes in many cases do not provide clues about the underlying molecular defect, thus unbiased genetic experiments in experimentally tractable organisms are required to establish Human disease or biomedical research Most recent reviews or relevant papers Microbial infections and host-pathogen interactions Cardenal-Muñoz et al, 2018;Swart et al, 2018;Steiner et al 2018;Koliwer-Brandl et al 2019;Brenz et al 2017 Mitochondrial diseases Chen et al 2017Chen et al , 2018Annesley et al 2014 Neuronal lipoid lipofuscinosis McLaren et al 2019;Smith et al, 2019 Poly-Q diseases Santarriaga et al 2018; Shwachman-Bodian-Diamond syndrome Weis et al, 2015 Pharmacogenetic research Wauters et al, 2019;Cocorocchio et al 2018;Kubohara and Kikuchi, 2018;Kubohara et al 2019;Arioka et al 2017;Dubois et al 2016…”

Section: Is There a Future For Dictyostelium As A Model Organism?mentioning

confidence: 99%

The past, present and future of Dictyostelium as a model system

Bozzaro¹

2019

Int. J. Dev. Biol.

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The social amoeba Dictyostelium discoideum has been a preferred model organism during the last 50 years, particularly for the study of cell motility and chemotaxis, phagocytosis and macropinocytosis, intercellular adhesion, pattern formation, caspase-independent cell death and more recently autophagy and social evolution. Being a soil amoeba and professional phagocyte, thus exposed to a variety of potential pathogens, D. discoideum has also proven to be a powerful genetic and cellular model for investigating host-pathogen interactions and microbial infections. The finding that the Dictyostelium genome harbours several homologs of human genes responsible for a variety of diseases has stimulated their analysis, providing new insights into the mechanism of action of the encoded proteins and in some cases into the defect underlying the disease. Recent technological developments have covered the genetic gap between mammals and non-mammalian model organisms, challenging the modelling role of the latter. Is there a future for Dictyostelium discoideum as a model organism? Peculiarities and advantages of Dictyostelium discoideum as model organismAmong the non-mammalian model organisms, Dictyostelium discoideum (in the following Dictyostelium) is unique, due to cell division and development being totally uncoupled, and because of the transition from a unicellular to a multicellular stage during the life cycle. Growing cells proliferate by binary fission but do not differentiate, whereas starving cells undergo multicellular development and differentiation without dividing and without any need for external nutrients. Thus growth and development can be studied separately, and several non-lethal mutants can be isolated

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“…DIF-1 is one of the most well-characterized differentiationinducing molecules in Dictyostelium. There are many reviews concerning experiments of DIF-1, including some on various biomedical activities in mammalian cell lines (Williams, 2006;Kay and Thompson, 2009;Fukuzawa, 2011;Kubohara and Kikuchi, 2018). Therefore, here we focus on the biosynthetic pathway of DIF-1 and the function of DIF-1, which was revealed by the knockout mutants of biosynthetic enzyme genes (Fig.…”

Section: Dif-1: Biosynthesis and Inactivationmentioning

confidence: 99%

Small molecules and cell differentiation in Dictyostelium discoideum

Araki¹,

Saito²

2019

Int. J. Dev. Biol.

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Dictyostelium is a microorganism found in soils that are known as the battle fields of chemical warfare. Genome analysis of Dictyostelium revealed that it has great potential for the production of small molecules, including secondary metabolites such as polyketides and terpenes. Polyketides are a large family of secondary metabolites which have a variety of structures. In accordance with their structural variety, polyketides have a plethora of biological activities, including antimicrobial, antifungal, and antitumor activities. Unsurprisingly, they have exceptional medical importance. Polyketides in nature work as protective compounds and /or function in pheromonal communication. Terpenes belong to another family of structurally diverse secondary metabolites which play roles in ecological interactions, including defence against predators and formation of mutually beneficial alliance with other organisms. Polyketides and terpenes work as intra-or inter-species signalling compounds, i.e. they play the role of a chemical language. However, in Dictyostelium, they work as paracrine signalling compounds which control the organism's multicellular morphogenesis. This review is primarily focused on the small molecules that regulate pattern formation in the slug stage of the organism and their biosynthetic pathways. Current in vivo understandings of polyketide DIF-1 induced cell differentiation and DIF-1-dependent/independent pathways are also discussed.

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Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Cited by 23 publications

References 114 publications

Synthesis of Dibenzofuran Derivatives Possessing Anticancer Activities: A Review

Synthesis of Dibenzofuran Derivatives Possessing Anticancer Activities: A Review

The past, present and future of Dictyostelium as a model system

Small molecules and cell differentiation in Dictyostelium discoideum

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