Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives: assessment of their antimicrobial, antituberculosis and antioxidant activity

Abstract

A new series of pyrazolo [1,2-b]phthalazine derivatives (4a-p) bearing the 5-aryloxypyrazole nucleus was synthesized by one-pot, three-component, base-catalyzed cyclo condensation reaction of 3-methyl-5-aryloxy-1-aryl-1H-pyrazole-4-carbaldehyde (1a-d), malononitrile or ethyl cyanoacetate (2a-b) and 2,3-dihydro-1,4-phthalazinedione (3a-b) in ethanol containing an eco friendly base, NaOH, in good to excellent yields. All synthesized compounds (4a-p) were duly characterized by physicochemical parameters, 1 H NMR, 13 C NMR, FT-IR and LCMS techniques. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 4e, 4g, 4h, 4k and 4o exhibited excellent antimicrobial activity compared with first line drugs. In vitro antituberculosis activity was evaluated against Mycobacterium tuberculosis H37Rv, and compounds 4g and 4o emerged as the promising antimicrobial members with better antituberculosis activity. A brine shrimp bioassay was carried out to study the in vitro cytotoxic properties of the synthesized compounds. In vitro antioxidant activity was evaluated by the ferricreducing antioxidant power method. Compounds 4c, 4d, 4g and 4h showed the highest antioxidant potencies.

Phthalazines and phthalazine hybrids as antimicrobial agents: Synthesis and biological evaluation

“…Phthalazine and phthalazine hybrid structures, in which a phthalazine moiety is attached to another heterocycle, are considered to be of immense importance owing to their wide spectrum of biological activities. 1,2,10 Accordingly, the in vitro antimicrobial activity of the newly synthesized heterocycles was appraised against two Gram-positive bacteria, namely, Bacillus subtilis and Staphylococcus aureus, in addition to two Gram-negative bacteria, namely, Pseudomonas aeruginosa and Escherichia coli.…”

“…5 Phthalazine derivatives are also considered as p38MAP kinase inhibitors, 6 selective binders of gamma-aminobutyric acid (GABA) receptors, 7 cyclooxygenase-2 (COX-2) inhibitors, 8 and high-affinity ligands of voltages gated calcium channels. 9 Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as antimicrobial, [10][11][12] antidiabetic, 13 analgesic, 14,15 anticonvulsant, 16,17 antitumor, [18][19][20] antiproliferative, 20 antiepileptic, 21,22 anti-inflammatory, 23,24 and vasorelaxant. 25,26 In addition, phthalazines are known as serotonin reuptake inhibitors and are considered as anti-depression agents.…”

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

“…Recently, Sangani et al . reported one‐pot synthesis of pyrazolo[1,2‐ b ]phthalazine‐5,10‐diones as antimicrobial, antituberculosis, and antioxidant agents.…”

Synthesis, characterization, X-ray structure, optical properties and theoretical calculations of condensed phthalazines

“…Phthalazine belongs to the azine class of molecules. It is an important group of heterocyclic compound which contains bridgehead hydrazine in a fused ring system and has a wide range of pharmaceutical and biological activities such as antitumor, 1 antimicrobial, 2 antifungal, 3 anti-inflammatory, 4 antioxidant activities 5 and vasorelexant effect. 6 In addition, these compounds are promising materials for the development of new luminescent materials and fluorescence probes.…”