Synthesis and Investigation of Phthalazinones as Antitubercular Agents

Santoso, Kristiana T.; Cheung, Chen‐Yi; Hards, Kiel; Cook, Gregory M.; Stocker, Bridget L.; Timmer, Mattie S. M.

doi:10.1002/asia.201801805

Cited by 9 publications

(4 citation statements)

References 44 publications

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“…The hit 30 is a phthalazin‐1(2H)‐one derivative. The phthalazin‐1(2H)‐one derivatives possess a variety of bioactivities, such as antibacterial, 43 antitubercular, 44 antinociceptive, 45 and anticancer 46,47 activities. The interaction between the active site residues of tubulin and the two hits was analyzed, and further compared with standard drug paclitaxel.…”

Section: Resultsmentioning

confidence: 99%

Discovery of novel tubulin inhibitors targeting taxanes site by virtual screening, molecular dynamic simulation, and biological evaluation

Zhang

Mao

Yang

et al. 2021

J of Cellular Biochemistry

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Microtubules play crucial role in process of mitosis and cell proliferation, which have been considered as attractive drug targets for anticancer therapy. The aim of this study was to discover novel and chemically diverse tubulin inhibitors for treatment of cancer. In this investigation, the multilayer virtual screening methods, including common feature pharmacophore model, structure-based pharmacophore model and molecular docking, were developed to screen BioDiversity database with 30,000 compounds. A total of 102 compounds were obtained by the virtual screening, and further filtered by diverse chemical clusters with desired properties and PAINS analysis. Finally, 50 compounds were selected and submitted to the biological evaluation. Among these hits, hits 8 and 30 with novel scaffolds displayed stronger antiproliferative activity on four human tumor cells including Hela, A549, MCF-7, and HepG2. Moreover, the two hits were subsequently submitted to molecular dynamic simulations of 90 ns with the aim of exploring the stability of ligandprotein interactions into the binding pocket, and further probing the mechanism of the interaction between tubulin and hits. The molecular dynamic simulation results revealed there had stronger interactions between tubulin and hits in equilibrium state. Therefore, the hits 8 and 30 have been well characterized as lead compounds for developing new tubulin inhibitors with potential anticancer activity.

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Section: Resultsmentioning

confidence: 99%

Discovery of novel tubulin inhibitors targeting taxanes site by virtual screening, molecular dynamic simulation, and biological evaluation

Zhang

Mao

Yang

et al. 2021

J of Cellular Biochemistry

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“…Abdelgawad and co-workers synthesized a series of phthalazone-tethered 1,2,3-triazole derivatives 517-518 by click cycloaddition reaction of alkyne-functionalized phthalazone 516 with different functionalized azides [169][170][171][172][173] in the presence of CuSO 4• 5H 2 O, sodium ascorbate and tris(benzyltriazolylmethyl)amine in H 2 O/tBuOH/CH 2 Cl 2 (Scheme 52). 174 Compounds 517-518 were tested for their biological activity and compound 518 was found to have antiproliferative activity.…”

Section: Scheme 51 Synthesis Of Compounds 515a-zjmentioning

confidence: 99%

Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry

Singh

Tyagi

Mishra

et al. 2023

SynOpen

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Carbohydrates, traditionally known for their energy-providing role, have gained significant attention in drug discovery due to their diverse bioactivities and stereodiversity. However, pure carbohydrate molecules often exhibit limited bioactivity and suboptimal chemical and physical characteristics. To address these challenges, functional groups with bioactive scaffolds have been incorporated into carbohydrate to enhance their bioactivity and improve their overall properties. Among the various synthetic methods available, click chemistry has emerged as a powerful tool for the synthesis of carbohydrate-containing bioactive scaffolds, known as glycohybrids. Click chemistry offers several advantages, including high chemo- and regioselectivity, mild reaction conditions, easy purification and compatibility with multiple functional groups. In the present review, we have emphasized the recent advances and most pertinent research on the development of 1,2,3-triazole-containing glycohybrids using click reaction, their biological evaluations and the structure-activity relationship during 2017-2023. These newly synthesised glycohybrids could potentially be developed as new chemical entities (NCE) in pharmaceutical chemistry and may encourage the use of carbohydrates in drug discovery processes. 1 Introduction 2 CuAAC click chemistry mediated synthesis of triazole based glycohybrids and their biological activities 3 Conclusions and perspective

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“…Specifically, as the synthesis of 3‐unsubstituted phthalides is regarded, the representative synthetic methods include cyclocarbonylation of ortho ‐halobenzyl alcohol, [ 5 ] oxidation of phthalyl alcohol, [ 6 ] Cannizzaro‐type lactonization of dialdehyde, [ 7 ] reduction of phthalic anhydride, [ 8 ] oxidative annulation of ortho ‐methyl benzoic acid, [ 9 ] [2+2+2] cycloaddition of 1,6‐diyne, [ 10 ] and so on (Scheme 1a). Normally, in these reactions, advanced functionalized substrates are demanded.…”

Section: Figurementioning

confidence: 99%