Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• . Antimalarial activity was significantly reduced when C-8 of the triazolopyrazine scaffold was substituted with CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects. Keywords: antimalarial; characterisation; DiversinateTM; fluorine

• and death, as 80% of deaths in this region were children under five [1]. Whilst there are drugs available for the treatment of malaria infections, most have now succumbed to parasite drug resistance and thus reduced clinical efficacy [2][3]. Consequently, new antiplasmodial drugs with novel malaria

• which antiplasmodial testing could not have been performed. Funding The authors acknowledge the Australian Research Council (ARC) for support towards NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908). The authors acknowledge the National Health and Medical Research Council (NHMRC

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• 210009, China Taizhou Medical Hi-Tech Development Public Services Platform, Taizhou 225300, China 10.3762/bjoc.17.201 Abstract Hoshinoamides A, B and C, linear lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata, with potent antiplasmodial activity against chloroquine

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• bioactive molecules. They are also known to present valuable biological activities, such as anti-HBV (1) [44], anti-HIV (2) [45], antitumor (3) [46] and even antiplasmodial activities (4) [47] (Scheme 2A). Although these studied bioactive compounds do not directly represent the structural moieties obtained

• antiplasmodial activity (37–40) (Scheme 14A) [114]. The use of vanadium-mediated aminoalkylation led to the introduction of a morpholinomethyl moiety into the heteroaromatic ring in a single step instead of the 5 steps required in the previously used route, thus significantly shortening the synthetic route, and

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• screened for the synthesis of these rings [16][17]. Notably, triazole rings exhibit various medicinal applications, such as usages as anticancer [18] anti-HIV [19], antimalarial [20], antiplasmodial [21], and antibacterial agents [1][22]. Some significant triazole derivatives in this context are shown in

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• [2], antitumor [3], anti-HIV [4], inhibitor of Trypanosoma brucei [5], angiogenesis inhibitor [6], antiplasmodial antifolates [7], and antimicrobial [8]. Moreover, and in particular N2,6-disubstituted-1,3,5-triazine-2,4-diamines possess a wide range of chemotherapeutic activities [8][9][10][11

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• synthetic, oxoisoaporphine-like analogues were found to have strong DNA binding affinity and therefore high cytotoxicity [5] as well as antiplasmodial activity [6]. Besides menisporphine (2), the related oxoisoaporphine alkaloids dauriporphine (3), 6-O-demethylmenisporphine (4), dauriporphinoline (5) and

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• ], and antitumor activities [11]. For example, the natural alkaloids berberine (IV) and narciclasine (V) possess antiplasmodial and antiviral activity, respectively [12][13]. Indotecan (VI) and its analog idimitecan (VII) were identified as topoisomerase I inhibitors, and were promoted into phase I

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood. Keywords: antibiotic; antiplasmodial; coenzyme A; metathesis; pantothenate; Introduction Bacteria, fungi, and parasites are all rapidly acquiring resistance to

• ]. One successful research direction has been to revisit “older” unexploited structural classes of antimicrobials [2][3][4][5]. As first demonstrated in the 1970s [6], many pantothenamides show antimicrobial activity [7][8][9][10][11][12], including antibacterial, antifungal and/or antiplasmodial

• vitro antiplasmodial activity of compound 16 in growth medium containing pantetheinase (open symbols) or in medium in which the pantetheinase had been inactivated (dark symbols). The antiplasmodial activity of this compound can be antagonized by increasing the extracellular concentration of pantothenate

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• used in folk medicine for stimulation in the cure of some paralytic diseases [1] and for the treatment of fever [2]. In addition, antituberculous [3], antiplasmodial and cytotoxic [2] properties have been also described. The active constituents of the bark are mainly tetrahydroquinoline alkaloids such

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• and benzo[b]indolo[1,2-h]naphthyridine heterocycles in one-pot, multi-step cascade sequences [3]. These ring systems are not only of chemical interest but biological testing revealed promising in vitro antiplasmodial activity and anticancer activity in certain cases [3]. While the analogous base

• , selected compounds were assessed for in vitro antiplasmodial (Plasmodium falciparum; drug resistant K1 strain) activity [15], cell-based anticancer activity (cell lines: NCI-H187 small cell lung cancer, KB oral cavity cancer, and MCF-7 breast cancer) [16], and in vitro antitubercular activity

• (Mycobacterium tuberculosis) [17] (Table 2). Promising antiplasmodial activity was seen with the spirocyclic compound 12 (IC50 2.65 µg/mL, 6.25 µM) and the related indoloazepinoindol-17-one 17 in which the allylic substituents are effectively merged (minus the ether oxygen) and embedded in the 7-membered ring

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• -a]isoquinolinone which has been isolated from Berberis darwinii [1][2][3]. Cryptolepine is an indolo[3,2-b]quinolone alkaloid found in west African shrub Cryptolepis sanguinolenta, a plant used in traditional medicine for the treatment of malaria [3]. This alkaloid has shown potent antiplasmodial [4

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• cyclization. Keywords: antiplasmodial activities; Conrad–Limpach reaction; mitochondrial membrane potential; natural products; quinolones; total synthesis; Introduction The four aurachins A–D (1–4) were first isolated from the myxobacterium Stigmatella aurantiaca strain Sg a15 in 1987 (Figure 1) [1]. This

• work [15]. In addition, many N-hydroxyquinolone derivatives with variable side chains displayed strong antiplasmodial activity at IC50 of ca. 1 nM [16]. In fact, owing to their occurrence in many natural products [17][18] and to the high frequency of their biological activities, compounds containing

• -resistant Plasmodium falciparum FcB1 and on Trypanosoma brucei gambiense. Aurachin D (4) and its geranyl analogue 9 showed a strong antiplasmodial activity at 0.04 and 0.07 µg/mL, respectively, while analogues 10, 11 and 17–19 were 10- to 100-fold less active (Table 3). Based on the simplest but less active

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• biological activity. Biflavonoids with anti-inflammatory [1][2][3], antileishmanial [4][5], antiplasmodial [6][7][8], antiviral [9] and β-secretase inhibitory [10] activity, amongst others, have been reported. The activity of the biflavonoids is in general much higher than that of the individual monomers [11

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• tetracyclic quinoline systems on privileged templates have significant biological properties, such as antitumoral [5][6], anti-inflammatory [7], antimalarial [8], antituberculosis [9], and antiplasmodial [10] activities. Accordingly, the synthesis of new families of such quinoline systems still attracts much

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• )methyl]aziridines by Cu(I)-catalyzed azide-alkyne cycloaddition, followed by microwave-assisted, regioselective ring opening by dialkylamine towards 1-(2,3-diaminopropyl)-1,2,3-triazoles. Although most of these compounds exhibited weak antiplasmodial activity, six representatives showed moderate

• antiplasmodial activity against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with IC50-values of ≤25 μM. Keywords: aminopropanes; antimalarial activity; aziridines; β-lactams; ring opening; Introduction Malaria remains a major issue in health control, especially in

• , which were shown to be of great importance as novel antiplasmodial agents (Figure 1) [6]. More recently, we reported 1,2,3-triaminopropanes 2 as a new class of antimalarial compounds (Figure 1), prepared through microwave-assisted, regioselective ring opening of the corresponding 2-(aminomethyl

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC50 of 12.1 µM. Marilone

• structural skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique reactions in fungal secondary metabolism. Marilone A (1) exhibited antiplasmodial activity against Plasmodium berghei with an IC50 of 12.1 µM. Marilone B (2) showed a specific antagonistic effect on

• proven for the analogous, nitrogen-containing compounds, i.e., phthalimidine derivatives isolated from the same fungus (Almeida et al., unpublished data). Marilones A, B and C (1–3) were tested for antiplasmodial activity, and marilone A exhibited an IC50 of 12.1 µM against the liver stage of Plasmodium