Squaramide Tethered Clindamycin, Chloroquine, and Mortiamide Hybrids: Design, Synthesis, and Antimalarial Activity

Tremblay, Thomas; Bergeron, Chantal; Gagnon, Dominic; Bérubé, Christopher; Voyer, Normand; Richard, Dave; Giguère, Denis

doi:10.1021/acsmedchemlett.2c00531

Cited by 3 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, two effective molecules against P. falciparum , the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik [ 80 ] and mortiamides isolated from Mortierella found in Nunavut [ 87 ], have been recently brought to light.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, mortiamides isolated from Mortierella species found in marine sediments from Northern Canada have been tested and have shown promising antiplasmodial activity ( Table 3 ) [ 85 , 86 ]. Alongside this, clindamycin, a structural analogue of mortiamides, has also been investigated [ 87 ]. Compounds from the Antarctic deep-sea octocoral Cnidaria , like keikipukaldes, pukalide aldehyde and norditerpenoid ineleganolide, have been proven to be active against Leishmania donovani ( Table 1 ) [ 62 ].…”

Section: The Paradigm Of Using Molecules Extracted From Northern Cana...mentioning

confidence: 99%

See 1 more Smart Citation

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

Bourgeois,

Lemos,

Roucheray

et al. 2024

Infectious Disease Reports

Self Cite

View full text Add to dashboard Cite

Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Paradigm Of Using Molecules Extracted From Northern Cana...mentioning

confidence: 99%

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

Bourgeois,

Lemos,

Roucheray

et al. 2024

Infectious Disease Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, a number of antibiotics have been developed based on them, such as levofloxacin [3,4], moxifloxacin [5], gemifloxacin [6,7], ciprofloxacin [8,9], and so on (Figure 1). Quinoline derivatives are also compounds used as antimalarial drugs, and chloroquine [10], quinine [11], and primaquine [12] have traditionally been used. In recent years, quinoline derivatives such as bosutinib [13], lenvatinib [14], and cabozantinib [15] have been employed clinically as anticancer agents (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Azuleno[2,1-b]quinolones and Quinolines via Brønsted Acid-Catalyzed Cyclization of 2-Arylaminoazulenes

Shoji,

Takeuchi,

Uda

et al. 2023

Molecules

View full text Add to dashboard Cite

Quinolone and quinoline derivatives are frequently found as substructures in pharmaceutically active compounds. In this paper, we describe a procedure for the synthesis of azuleno[2,1-b]quinolones and quinolines from 2-arylaminoazulene derivatives, which are readily prepared via the aromatic nucleophilic substitution reaction of a 2-chloroazulene derivative with several arylamines. The synthesis of azuleno[2,1-b]quinolones was established by the Brønsted acid-catalyzed intramolecular cyclization of 2-arylaminoazulene derivatives bearing two ester groups at the five-membered ring. The halogenative aromatization of azuleno[2,1-b]quinolones with POCl3 yielded azuleno[2,1-b]quinolines with a chlorine substituent at the pyridine moiety. The aromatic nucleophilic substitution reaction of azuleno[2,1-b]quinolines bearing chlorine substituent with secondary amines was also investigated to afford the aminoquinoline derivatives. These synthetic methodologies reported in this paper should be valuable in the development of new pharmaceuticals based on the azulene skeleton.

show abstract

Real-Time Imaging of Antimalarial Drug Effects onPlasmodium falciparum-Infected Red Blood Cells

Wallner,

Bonsen,

Mathis

et al. 2024

Preprint

View full text Add to dashboard Cite

Malaria remains a significant global health challenge, exacerbated by emerging drug resistance, which has been recurring ever since Chloroquine resistance was reported to spread in the 1960s. Cabamiquine (M5717), a promising antimalarial candidate, targets Plasmodium falciparum elongation factor 2 (PfeEF2) and has demonstrated high potency and multi-stage activity. However, differences in parasite-killing kinetics require further exploration. This proof-of-concept study employs time-lapse microscopy to assess the effects of Chloroquine and Cabamiquine on P. falciparum-infected red blood cells. Using a fluorogenic DNA dye, we monitored morphological changes and cell death at the single-cell level. Unlike the faster-killing Chloroquine, our findings confirm a lag phase of the effect of Cabamiquine and reveal a delay before host cell lysis. This delayed cytotoxic effect underscores the cytostatic phase of the drug prior to killing and highlights its potential in combination therapies. Our novel imaging approach provides a comprehensive fingerprinting method to quantify cytostatic, cytotoxic, and cytolytic activities of antimalarial drugs, offering valuable insights into their mechanisms of action at a cellular level therefore enabling to discriminate the steps prior to parasite clearance in hosts.

show abstract

Squaramide Tethered Clindamycin, Chloroquine, and Mortiamide Hybrids: Design, Synthesis, and Antimalarial Activity

Cited by 3 publications

References 46 publications

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

Synthesis of Azuleno[2,1-b]quinolones and Quinolines via Brønsted Acid-Catalyzed Cyclization of 2-Arylaminoazulenes

Real-Time Imaging of Antimalarial Drug Effects onPlasmodium falciparum-Infected Red Blood Cells

Contact Info

Product

Resources

About