Synthesis and Antimalarial Activity of Some Neocryptolepine Analogues Carrying a Multifunctional Linear and Branched Carbon-Side Chains

Shaban, Elkhabiry; Wicht, Kathryn J.; Wang, N.; Mei, Zhen-Wu; Hayashi, Ikuya; Gokha, Ahmed Abdel Aleem El; Kaiser, Marcel; Sayed, Ibrahim El Tantawy El; Egan, Timothy J.; Inokuchi, Tsutomu

doi:10.3987/com-14-12948

Cited by 11 publications

(7 citation statements)

References 23 publications

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“…Furthermore, sulfonylated compound 50 exhibited high potency against various L6 cell lines (18.2 nM) and against NF54 cells (malaria parasites, 14.2 nM), but poor selectivity (SI= 1.3; SI= cytotoxicity/antiplasmodial activity ratio). Compound 50 was approximately 200 times more potent than the parent neocryptolepine, 16 times more potent than the nonsulfonylated precursor 51 [69], and with a potency comparable to podophylotoxin (14.5 nM against L6 cells) [70]. Furthermore, the synthesis and evaluation of the isosteric 11aminoalkylamino-substituted chromeno[2,3-b]indoles revealed that the N5-Me group is highly relevant for optimum activity [44].…”

Section: Cytotoxic Activitymentioning

confidence: 98%

“…Furthermore, several 11-amino derivatives of neocryptolepine were synthesized and tested against T. cruzi and T. brucei (Table 3) [69]. Data on neocryptolepine are also available [74b,76].…”

Section: Antiprotozoal Activitymentioning

confidence: 99%

“…On the other hand, leishmaniasis is a vector-transmitted protozoal disease that currently affects 12 million people in 88 countries. Interestingly, neocryptolepine also exhibited weak activity against Leishmania donovani, with IC 50 = 49.5 ± 3.7 μM (Table 3) [69], almost two orders of magnitude higher than the standard miltefosine (67, IC 50 = 0.56 ± 0.07 μM) [74b]. Neocryptolepine and other quinoline alkaloids have shown notable docking to LmajMetRS, a protein from Leishmania major [79].…”

Section: Antiprotozoal Activitymentioning

confidence: 99%

“…In 2013, the effects simultaneously of changing the side chains at the C-11 position and modifying the nature of the C-2 substituent were examined [69]. The C-11 basic side chains examined included alkylamino and ωaminoalkylamino versions, as well as acyclic or cyclic carbamides or thiocarbamides (Table 7).…”

Section: Antimalarial Activitymentioning

confidence: 99%

“…The synthesis and in vitro antimalarial activity of analogues carrying linear and branched dibasic side chains at C-11 revealed that a branched structural motif is not superior for antimalarial activity over a linear side chain in the antimalarial test against the chloroquine-sensitive P. falciparum strain NF54 [69]. It was also observed that a three-carbon atom chain separating both nitrogen atoms was the most appropriate.…”

Section: Antimalarial Activitymentioning

confidence: 99%

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Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs

Larghi¹,

Bracca²,

Aguilar³

et al. 2015

CTMC

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Plants are one of the most important resources for the discovery of new drugs. The potential of natural compounds as new drug leads is clearly illustrated by the discovery and development of many modern medicines. This is an encouraging factor that drives natural products research in the vegetable kingdom. Neocryptolepine is a tetracyclic nitrogen heterocycle isolated from the African climber Cryptolepis sanguinolenta, which is widely used in traditional African medicine in many countries of Central and West Africa. The natural product is one of the representative examples of the small family of indolo[2,3-b]quinoline alkaloids, being endowed of multiple biological activities, including DNA-binding and inhibition of the enzyme topoisomerase II. It is also cytotoxic, antibacterial, antifungal and molluscicidal, also displaying antiprotozoal activity, particularly as antitrypanosomal, antileishmanial, antischistosomal and antiplasmodial. Some of these activities have been related to the product's ability to bind to DNA and to inhibit topoisomerase II; however, the exact mechanisms behind all of the observed bioactivities have not been comprehensively clarified. Major research activities regarding neocryptolepine have been focused into two seemingly opposite fields, related to its cytotoxic and antimalarial properties. Optimization of the natural product as a cytotoxic agent implied improvements in its bioavailability and activity, while the need of non-cytotoxic compounds guided the design and optimization of antimalarial agents. Therefore, the aim of the present article is to systematically review the current knowledge about the diversity of the biological activities related to neocryptolepine, its analogs and derivatives.

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Section: Cytotoxic Activitymentioning

confidence: 98%

Section: Antiprotozoal Activitymentioning

confidence: 99%

Section: Antiprotozoal Activitymentioning

confidence: 99%

Section: Antimalarial Activitymentioning

confidence: 99%

Section: Antimalarial Activitymentioning

confidence: 99%

See 3 more Smart Citations

Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs

Larghi¹,

Bracca²,

Aguilar³

et al. 2015

CTMC

View full text Add to dashboard Cite

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Indoloquinoline Alkaloids as Antimalarials: Advances, Challenges, and Opportunities

Parvatkar,

Diagne,

Zhao

et al. 2024

ChemMedChem

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Malaria infections affect almost half of the world's population, with over 200 million cases reported annually. Cryptolepis sanguinolenta, a plant native to West Africa, has long been used across various regions of Africa for malaria treatment. Chemical analysis has revealed that the plant is abundant in indoloquinolines, which have been shown to possess antimalarial properties. Cryptolepine, neocryptolepine, and isocryptolepine are well‐studied indoloquinoline alkaloids known for their potent antimalarial activity. However, their structural rigidity and associated cellular toxicity are major drawbacks for preclinical development. This review focuses on the potential of indoloquinoline alkaloids (cryptolepine, neocryptolepine, and isocryptolepine) as scaffolds in drug discovery. The article delves into their antimalarial effects in vitro and in vivo, as well as their proposed mechanisms of action and structure‐activity relationship studies. Several studies aim to improve these leads by reducing cytotoxicity while preserving or enhancing antimalarial activity and gaining insights into their mechanisms of action. These investigations highlight the potential of indoloquinolines as a scaffold for developing new antimalarial drugs.

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Neocryptolepine (Cryprotackieine), A Unique Bioactive Natural Product: Isolation, Synthesis, and Profile of Its Biological Activity

et al. 2014

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Synthesis and Antimalarial Activity of Some Neocryptolepine Analogues Carrying a Multifunctional Linear and Branched Carbon-Side Chains

Cited by 11 publications

References 23 publications

Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs

Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs

Indoloquinoline Alkaloids as Antimalarials: Advances, Challenges, and Opportunities

Neocryptolepine (Cryprotackieine), A Unique Bioactive Natural Product: Isolation, Synthesis, and Profile of Its Biological Activity

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