7‐Chloroquinoline–isatin Conjugates: Antimalarial, Antitubercular, and Cytotoxic Evaluation

Raj, Raghu; Biot, Christophe; Carrère-Kremer, Séverine; Kremer, Laurent; Guérardel, Yann; Gut, Jiří; Rosenthal, Philip J.; Forge, Delphine; Kumar, Vipan

doi:10.1111/cbdd.12273

Cited by 61 publications

(32 citation statements)

References 50 publications

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“…Hybrids with a linker chain length of greater than three were found to be less potent than chloroquine. The members of the O'Neill group, which worked on synthetic 1,2,4-trioxolaquines (91), and several others (62,92), have reported similar results. Therefore, the length and nature of the linker exert a strong influence on the antimalarial efficacy of the conjugates.…”

Section: Linker Selectionmentioning

confidence: 71%

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

Agarwal

Gupta

Awasthi

2017

Antimicrob Agents Chemother

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Emergence of drug-resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected toward finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. In light of this situation, scientists have come up with the concept of hybridization of two or more active pharmacophores into a single chemical entity, resulting in "antimalarial hybrids." The approach has been applied widely for generation of lead compounds against deadly diseases such as cancer and AIDS, with a proven potential for use as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery. A sudden surge has been evidenced in the number of studies on the design and synthesis of hybrids for treating malaria and may be regarded as proof of their potential advantages over artemisinin-based combination therapy (ACT). However, it is evident from recent studies that most of the potential advantages of antimalarial hybrids, such as lower toxicity, better pharmacokinetics, and easier formulation, have yet to be realized. A number of questions left unaddressed at present need to be answered before this approach can progress to the late stages of clinical development and prove their worth in the clinic. To the best of our knowledge, this compilation is the first attempt to shed light on the shortcomings that are surfacing as more and more studies on molecular hybridization of the active pharmacophores of known antimalarials are being published.

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Section: Linker Selectionmentioning

confidence: 71%

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

Agarwal

Gupta

Awasthi

2017

Antimicrob Agents Chemother

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“…A previous report from our group revealed the synthesis and antimalarial evaluation of 1H-1,2,3-triazole-tethered-7chloroquinoline-isatin [40,41] and piperazine-tethered isatin-7chloroquinoline conjugates [42]. The observed activity profiles among these conjugates were found to depend on the substituent at the C-5 position of isatin and the length of the alkyl chain.…”

Section: Introductionmentioning

confidence: 93%

β-amino-alcohol tethered 4-aminoquinoline-isatin conjugates: Synthesis and antimalarial evaluation

Nisha

Gut

Rosenthal

et al. 2014

European Journal of Medicinal Chemistry

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A series of β-amino alcohol tethered 4-aminoquinoline-isatin conjugates were synthesized with the aim of probing their antimalarial structure activity relationship. Two of the most active conjugates (11b and 11f) exhibited antimalarial efficacy comparable to that of chloroquine, with IC50 values of 11.8 and 13.5 nM, respectively against chloroquine resistant W2 strain of Plasmodium falciparum and are devoid of any cytotoxicity.

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“…CQ-isatin hybrids have been reported as potent antimalarial agents (Chiyanzu et al, 2005;Lunt et al, 2010;Raj et al, 2014). Raj et al (2013) synthesized a series of triazole linked 7-chloroquinoline and isatin hybrids.…”

Section: Learning From the Cq Hybrid Approach For Antimalarial Drug Dmentioning

confidence: 99%