Recent developments in antimalarial activities of 4-aminoquinoline derivatives

Ravindar, Lekkala; Hasbullah, Siti Aishah; Rakesh, K.P.; Hassan, Nurul Izzaty

doi:10.1016/j.ejmech.2023.115458

Cited by 23 publications

(2 citation statements)

References 101 publications

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“…This structural modification might have contributed to the decrease in the observed antiprotozoal activity of compound Z, compared to their counterparts X and Y. Even though there is reported evidence that the presence of OH groups tends to increase the antiprotozoal activity of bioactive compounds [58], other reports highlight a different opinion on this matter [59].…”

Section: Resultsmentioning

confidence: 99%

Target-Based 6-5 Fused Ring Heterocyclic Scaffolds Display Broad Antiparasitic Potency In Vitro

Dize,

Tali,

Ngansop

et al. 2024

Future Pharmacology

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Malaria, leishmaniasis, and African trypanosomiasis are protozoan diseases that constitute major global health problems, especially in developing countries; however, the development of drug resistance coupled with the toxicity of current treatments has hindered their management. The involvement of certain enzymes (dihydrofolate reductase [DHFR]) or proteins (potassium channels) in the pathogenesis of these protozoan diseases is undeniable. In this study, a series of three DHFR inhibitors (6-5 fused heterocyclic derivatives X, Y, and Z) and one K+ channel blocker (E4031) were screened for their inhibitory effects on Leishmania donovani, Plasmodium falciparum, and Trypanosoma brucei. A resazurin assay was used to assess the antitrypanosomal and antileishmanial activities of the test compounds, whereas the antiplasmodial activity was evaluated through the SYBR Green I test. Moreover, the cytotoxicities of the test compounds were evaluated in Vero, Raw 264.7, and HepG-2 cells using a resazurin-based test, while their pharmacokinetic properties were predicted using the online tool, pkCSM. As a result, compound Y exhibited selective (selectivity index range: from 2.69 to >61.4; Vero, Raw 264.7, and HepG-2 cells) and broad-spectrum antiprotozoal activity against L. donovani promastigotes (IC50: 12.4 µM), amastigotes (IC50: 4.28 µM), P. falciparum (IC50: 0.028 µM), and T. brucei brucei (IC50: 0.81 µM). In addition, compound X inhibited the growth of P. falciparum (IC50: 0.0052 µM) and T. brucei brucei (IC50: 6.49 µM). In silico screening of the active antiprotozoal compounds revealed positive drug likeness scores, as none of the criteria for Lipinski’s rule were violated by these compounds. However, in-depth pharmacokinetic and mechanistic studies are warranted to support the discovery of novel antiprotozoal agents against malaria, leishmaniasis, and African trypanosomiasis by repurposing K+ channel blockers and DHFR inhibitors.

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Section: Resultsmentioning

confidence: 99%

Target-Based 6-5 Fused Ring Heterocyclic Scaffolds Display Broad Antiparasitic Potency In Vitro

Dize,

Tali,

Ngansop

et al. 2024

Future Pharmacology

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“…[22] Quinoline and side-chain analogues contribute a centric role in providing huge quinoline-based medications with a significant contribution in the new anti-malarial drug development. [23] Apart from quinolines, [24] other nitrogen, nitrogen/ sulphur/ oxygen containing heterocycles [11] such as indole, [25] phenothiazine, [26] triazoles, [14] β-carboline, [27,28] have also been well explored.…”

Section: Heterocycles As Privileged Scaffold Towards Anti-malarial Ag...mentioning

confidence: 99%

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Dhameliya,

Patel,

Kathuria

et al. 2024

ChemistrySelect

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Malaria remains a severe infectious disease caused by Plasmodium parasites among the primarily afflicting impoverished populations. According to World Health Organization (WHO) report, there were an estimated 247 million malarial cases globally, resulting in approximately 6,19,000 fatalities. Particularly prevalent in tropical and subtropical regions, the development of drug resistance has exacerbated this public health challenge. Consequently, there has been a concrete effort to explore novel compounds with anti‐malarial properties. In continuation of our previous works, this review focuses on heterocyclic compounds documented in 2021 and 2022, including artemisinin, benzimidazole, benzofuran, β‐lactam, coumarin, furan, indole, morpholine, piperazine, pyrimidine, quinoline, triazole, etc. highlighting their efficacy, structural characteristics, in vitro and in vivo activities, among other relevant aspects for the broad interest of medicinal chemists working on the design and development of novel anti‐malarial agents.

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Exploring the Recent Pioneering Developments of Small Molecules in Antimalarial Drug Armamentarium: A Chemistry Prospective Appraisal

Bagratee,

Prawlall,

Ndlovu

et al. 2024

Chemistry & Biodiversity

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Malaria is a very destructive and lethal parasitic disease that causes significant mortality worldwide, resulting in the loss of millions of lives annually. The uncontrolled intake of antimalarial drugs often employed in clinical settings has resulted in the emergence of numerous strains of plasmodium that are resistant to these drugs, including multidrug‐resistant strains. Hence, there is an urgent need for developing unique classes of antimalarial drugs that function with distinct mechanisms of action. In this context, the design and development of hybrid compounds that combine pharmacophoric properties from different lead molecules into a single unit gives a unique perspective towards further development of malaria drugs in the next generation. In light of this, we have reviewed the progress of hybrid antimalarial agents from 2021 up to the present. This manuscript presents a comprehensive overview of the latest advancements in the medicinal chemistry pertaining to small molecules, with a specific focus on their potential as antimalarial agents. This review explores a variety of physiologically active compounds that have been described in the literature in order to lay a strong foundation for the logical design and eventual identification of antimalarial drugs based on lead frameworks.

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Recent developments in antimalarial activities of 4-aminoquinoline derivatives

Cited by 23 publications

References 101 publications

Target-Based 6-5 Fused Ring Heterocyclic Scaffolds Display Broad Antiparasitic Potency In Vitro

Target-Based 6-5 Fused Ring Heterocyclic Scaffolds Display Broad Antiparasitic Potency In Vitro

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Exploring the Recent Pioneering Developments of Small Molecules in Antimalarial Drug Armamentarium: A Chemistry Prospective Appraisal

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