Tetrahydrobenzo[h]quinoline derivatives as a novel chemotype for dual antileishmanial-antimalarial activity graced with antitubercular activity: Design, synthesis and biological evaluation

Ibrahim, Tamer M.; Abada, Ghada; Dammann, Marcel; Maklad, Raed M.; Eldehna, Wagdy M.; Salem, Rofaida; Abdelaziz, Marwa M.; El-domany, Ramadan A.; Bekhit, Adnan A.; Beockler, Frank M.

doi:10.1016/j.ejmech.2023.115534

Cited by 7 publications

(1 citation statement)

References 66 publications

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“… 2023 ; Ibrahim et al. 2023 ; Boakye et al. 2023 ) (some of these have been recently reviewed in Panecka-Hofman et al.…”

Section: Dynamical Aspects Of the Ptr1-targeted Drug Designmentioning

confidence: 99%

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

Panecka-Hofman,

Poehner

2023

Eur Biophys J

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Pteridine reductase 1 (PTR1) is a folate and pterin pathway enzyme unique for pathogenic trypanosomatids. As a validated drug target, PTR1 has been the focus of recent research efforts aimed at finding more effective treatments against human parasitic diseases such as leishmaniasis or sleeping sickness. Previous PTR1-centered structural studies highlighted the enzyme characteristics, such as flexible regions around the active site, highly conserved structural waters, and species-specific differences in pocket properties and dynamics, which likely impacts the binding of natural substrates and inhibitors. Furthermore, several aspects of the PTR1 function, such as the substrate inhibition phenomenon and the level of ligand binding cooperativity in the enzyme homotetramer, likely related to the global enzyme dynamics, are poorly known at the molecular level. We postulate that future drug design efforts could greatly benefit from a better understanding of these phenomena through studying both the local and global PTR1 dynamics. This review highlights the key aspects of the PTR1 structure and dynamics relevant to structure-based drug design that could be effectively investigated by modeling approaches. Particular emphasis is given to the perspective of molecular dynamics, what has been accomplished in this area to date, and how modeling could impact the PTR1-targeted drug design in the future.

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“… 2023 ; Ibrahim et al. 2023 ; Boakye et al. 2023 ) (some of these have been recently reviewed in Panecka-Hofman et al.…”

Section: Dynamical Aspects Of the Ptr1-targeted Drug Designmentioning

confidence: 99%

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

Panecka-Hofman,

Poehner

2023

Eur Biophys J

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A simple, safe, eco‐friendly, and unique synthesis of hexahydro‐quinolines employing Fe₃O₄‐MWCNT@MnO₂ as a reusable catalyst

Rao,

Maddila,

Anantha

et al. 2024

Applied Organom Chemis

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This work aims to explore the catalytic potential of manganese oxide (MnO2) supported on (Fe3O4‐MWCNT) nano‐composite, which is composed of iron oxide and multi‐walled carbon nanotubes. The nano‐composite was synthesized using a simple impregnation technique. The catalyst material was extensively characterized using a variety of possible analytical methods, including X‐ray diffraction (XRD), Brunauer–Emmett–Teller (BET), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X‐ray spectroscopy (EDS). Then, utilizing a multi‐component condensation protocol comprising substituted aldehydes, cyclohexadione, ethylacetoacetate, and NH4OAc, the catalytic efficacy of the Fe3O4‐MWCNT@MnO2 nano‐composite was assessed for synthesizing novel hexahydro‐quinoline analogues. The catalyst was found to be effective because of its huge specific surface area, stability, porosity, and distinctive exposed surfaces. The catalyst's surface exhibited an exceptionally active nature, as seen by the notably high turnover frequency. Herein, we present a reusable and effective catalytic method that produces outstanding product yields (93%–97%) under mild reaction conditions, using ethanol as a green solvent. Cost‐effectiveness, environmental safety, and high atom efficiency are achieved using the nano‐composite.

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Design and synthesis of benzo[b]thiophene‐based hybrids as novel antitubercular agents against MDR/XDR Mycobacterium tuberculosis

Al‐Warhi,

Rashad,

Almahli

et al. 2023

Archiv der Pharmazie

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In an effort to support the global fight against tuberculosis (TB), which is widely recognized as the most lethal infectious disease worldwide, we present the design and synthesis of new benzo[b]thiophene‐based hybrids as promising candidates for the management of multidrug‐resistant (MDR)/extensively drug‐resistant (XDR) Mycobacterium tuberculosis. The isatin motif was incorporated into the target hybrids as it represents a privileged scaffold in antitubercular drug discovery. Since lipophilicity plays a pivotal role in the anti‐TB agents' activity, the lipophilicity of the target hybrids was manipulated via the development of two series of N‐1 methyl and N‐1 benzyl substituted isatins (6a–h and 9a–h, respectively). Screening of the target hybrids was first performed against drug‐sensitive M. tuberculosis (ATCC 25177). The structure–activity relationship outputs highlighted that incorporation of 3‐unsubstituted benzo[b]thiophene and 5‐methoxy isatin moieties was favorable for the antimycobacterial activity. Thereafter, the most potent molecules (6b–h, 9c–e, and 9h) were evaluated against the resistant strains MDR‐TB (ATCC 35822) as well as against XDR‐TB (RCMB 2674) where they displayed promising activity. To evaluate the safety of the target hybrids, an sulforhodamine B assay was conducted to determine their possible cytotoxic effects on VERO cells.

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Tetrahydrobenzo[h]quinoline derivatives as a novel chemotype for dual antileishmanial-antimalarial activity graced with antitubercular activity: Design, synthesis and biological evaluation

Cited by 7 publications

References 66 publications

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

A simple, safe, eco‐friendly, and unique synthesis of hexahydro‐quinolines employing Fe₃O₄‐MWCNT@MnO₂ as a reusable catalyst

Design and synthesis of benzo[b]thiophene‐based hybrids as novel antitubercular agents against MDR/XDR Mycobacterium tuberculosis

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Tetrahydrobenzo[h]quinoline derivatives as a novel chemotype for dual antileishmanial-antimalarial activity graced with antitubercular activity: Design, synthesis and biological evaluation

Cited by 7 publications

References 66 publications

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design

A simple, safe, eco‐friendly, and unique synthesis of hexahydro‐quinolines employing Fe3O4‐MWCNT@MnO2 as a reusable catalyst

Design and synthesis of benzo[b]thiophene‐based hybrids as novel antitubercular agents against MDR/XDR Mycobacterium tuberculosis

Contact Info

Product

Resources

About

A simple, safe, eco‐friendly, and unique synthesis of hexahydro‐quinolines employing Fe₃O₄‐MWCNT@MnO₂ as a reusable catalyst