Structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles

Rylands, Laa-iqa; Welsh, Athi; Maepa, Keletso; Stringer, Tameryn; Taylor, Dale; Chibale, Kelly; Smith, Gregory S.

doi:10.1016/j.ejmech.2018.10.019

Cited by 42 publications

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“…Recently, the research group of Smith reported a series of neutral, cyclometallated Ir(III)Cp* complexes (25), based on the 2-phenylbenzimidazole scaffold (24), showing in vitro antiplasmodial activity against NF54 and K1 strains of P. falciparum ( Figure 6) [31]. The synthesized complexes displayed activities in the low micromolar range against the tested strains.…”

Section: Benzimidazole (Hybrid) Ligandsmentioning

confidence: 99%

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

2020

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In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.

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Section: Benzimidazole (Hybrid) Ligandsmentioning

confidence: 99%

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

2020

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“…Benzimidazoles and 2‐aminobenzimidazoles are very powerful compounds because of their applications in therapeutic and biological sciences (Figure ) . These compounds were used as neuropeptide YY1 receptor antagonist, N ‐methyl‐D‐aspartate (NMDA) antagonist, factor Xa(FXa) inhibitor, poly(ADP‐ribose)polymerase (PARP) inhibitor and non‐peptide thrombin inhibitor .…”

Section: Figurementioning

confidence: 99%

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

2018

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The synthesis of aminobenzimidazoles has been demonstrated under mild reaction conditions using cobalt catalyst in one pot reaction. This methodology involved domino intra and intermolecular C-N cross-coupling reaction. In addition, functional group tolerance has been also explored.Benzimidazoles [1][2][3][4][5][6][7][8][9][10] and 2-aminobenzimidazoles [11][12][13][14][15][16][17][18][19][20][21] are very powerful compounds because of their applications in therapeutic [22][23] and biological sciences ( Figure 1). [24][25] These compounds were used as neuropeptide YY1 receptor antagonist, [26] N-methyl-D-aspartate (NMDA) antagonist, [27] factor Xa(FXa) inhibitor, [28] poly(ADP-ribose)polymerase (PARP) inhibitor [29] and non-peptide thrombin inhibitor. [30] In addition, these compounds show anti-inflammatory, antimicrobial and antibacterial activities. [31] Apart from that, these compounds can also be used for the synthesis of dyes and high-temperature resistance polymers. [32] Therefore, the construction of benzimidazole derivatives were developed by many researchers via both traditional methods [33][34][35] and C-N cross-coupling reactions using various transition metals such as Cu, [36][37][38][39][40] Pd, [41][42][43] Co, [44] Zn, [45][46][47] and Ru. [48] In this connection, we would like to demonstrate the methodology for the synthesis of benzimidazoles from thiourea in one pot reaction via desulphurization/substitution/domino C-N cross-coupling reaction using cobalt source as catalyst under mild reaction conditions.

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“…Various metals have been introduced in designing metal-organic framework in drug development, in which ruthenium is often considered as the most promising transition metal from the pharmaceutical viewpoint because of its safe and druggable properties (Maschke, Alborzinia, Lieb, Wölfl, & Metzler-Nolte, 2014;Meier et al, 2013). The ruthenium (Ru-based) compounds have also demonstrated promising biological activities such as antibacterial (F. Li, Collins, & Keene, 2015;Mu et al, 2018), antileishmanial (Iniguez et al, 2016;Marcusso Orsini et al, 2016), anticancer (Su, Li, & Li, 2018;Thota, Rodrigues, Crans, & Barreiro, 2018) and antiplasmodial (Ekengard et al, 2015;Rylands et al, 2019). Notably, reports revealed that Ru complexation improves the antiplasmodial activity in comparison to free ligands e.g.…”

Section: Introductionmentioning

confidence: 99%

Exploring Ruthenium-based organometallic inhibitors against Plasmodium Calcium Dependent Kinase 2 (PfCDPK2): a combined ensemble docking, QM paramterization and molecular dynamics study

Patel

Athar²,

Jha

2020

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Recent advances in the metal-organic framework (MOF) have accelerated the discovery of novel metal-based anticancer, antibacterial and antimalarial compounds. This is substantiated by many serendipitously discovered metals (Ru, Rh, and Ir) based inhibitors that established the importance of metal inserted into the known organic scaffold. Conversely, it is possible to design novel bioactive compounds by mimicking hypervalent carbon atoms by transition metals. This process can be facilitated by computational drug discovery by treating metal center using optimized parameters that can be used for molecular docking and molecular dynamics simulations. Further, the method can be plugged with high computational power and refined algorithms to interpret chemical phenomena with atomic-level insights. In the present work, we have demonstrated an approach for parameterizing three organometallic ligands (FLL, E52, and staurosporine) using MCPB.py. In particular, we report that E52 and FLL have a better shape complimentary and affinity compared to staurosporine identified inhibitor (staurosporine) against Calcium-dependent protein kinases 2 (CDPK2). This study also revealed that a flexible approach (ensemble) outperforms for the given target with dynamic movements. The calculated MMPBSA energies for staurosporine, FLL and E52 were −66.461 ± 2.192, −67.182 ± 1.971 and −91.339 ± 2.745 kcal/mol respectively.

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Structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles

Cited by 42 publications

References 42 publications

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

Exploring Ruthenium-based organometallic inhibitors against Plasmodium Calcium Dependent Kinase 2 (PfCDPK2): a combined ensemble docking, QM paramterization and molecular dynamics study

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