Synthesis and biological evaluation of novel isoxazole derivatives from acridone

Abstract

The present study was carried out in an attempt to synthesize a new class of potential antibacterial agents. In this context, novel isoxazoles were synthesized and evaluated for their potential antibacterial behavior against four pathogenic bacterial strains. The synthesized compounds exhibited moderate‐to‐good antibacterial activity against these strains. The highest antibacterial activity was observed against the Escherichia coli strains, particularly for compounds 4a and 4e with phenyl and para‐nitrophenyl groups on the isoxazole–acridone skeleton; they showed promising minimum inhibitory concentration values of 16.88 and 19.01 μg/ml, respectively, compared with the standard drug chloramphenicol (22.41 µg/ml). The synthesized compounds were subjected to in silico docking studies to understand the mode of their interactions with the DNA topoisomerase complex (PDB ID: 3FV5) of E. coli. The molecular docking results showed that compounds 4a–l occupy the active site of DNA topoisomerase (PDB ID: 3FV5), stabilized via hydrogen bonding and hydrophobic interactions, which may be the reason behind their interesting in vitro antibacterial activity.

A review of recent synthetic strategies and biological activities of isoxazole

“…Yazdani et al [29] first explored the potential of a 1,3-dipolar cycloaddition reaction that produces asymmetric dendrimer formation. It begins with the propargylation of pentaerythritol 1 with potassium hydroxide in S C H E M E 2 Preparation of 3, 5-disubstituted isoxazole derivatives [25] S C H E M E 3 Preparation of innovative acridone having isoxazoles [26] dry DMF and propargyl bromide 2 (Scheme 7), and the tetrapropargylated core 3 with the bromonitrile oxide precursor in THF at 45 C. It was monitored by the 1,3-bipolar cycloaddition reaction for 3 h, NaHCO 3 was used as the base and ZnCl 2 was used as the catalyst. 5,5 0 -(((2,2-bis(([3-bromoisoxazol-5-yl] methoxy)-methyl)propane-1,3-diyl)bis(oxy))-bis-(methylene))-bis(3-bromoisoxazole) 4 was obtained with an isolation yield of 44% (Scheme 7).…”

“…The reaction of quinoline-2-carbaldehyde oxime 1, in situ, created with nucleophilic addition of 2-methyl quinoline and TBN, undergoes formal 1,3-dipolar cycloaddition with alkenes 2 or alkynes 3 to obtain final product S C H E M E 5 Synthesis of isoxazoles having reversed regioselectivity [27] S C H E M E 4 SAR studies of new Isoxazole analogues [26] 3-(quinolin-2-yl)isoxazoles 4 under metal-free reaction conditions has been reported by Dahan Wang, et al [33] as depicted in Scheme 11.…”

Martynia annua safety and efficacy: heavy metal profile, in silico and in vitro approaches on antibacterial and antidiabetic activities

“…Choosing molecular target: The crystal protein structure of E.coli Topoisomerase IV (PDB ID: 3FV5) (Aarjane et al 2020) and crystal structure of Human Maltase-Glucoamylase (PDB ID: 3TOP) (Singh et al 2021) were obtained from the Protein Data Bank (PDB). 3FV5 is an X-ray crystallographic protein that is complexed with an inhibitor and has a resolution of 1.80.…”

Regioselective Synthesis of 3, 5‐Disubstituted Isoxazole Catalyzed by Cu2O−ZnO Nanocomposite

“…[1] Isoxazole is a five-membered heterocyclic scaffold commonly encountered in many natural products and drug molecules. [2] Derivatives of isoxazole exhibit a diverse range of biological and pharmacological activities such as antithrombotic, [3] antibacterial, [4] antagonist, [5] antiviral, [6,7] antitumor, [8] anti-HIV, [9] herbicidal, [10] insecticidal [11] and fungicidal. [12] Isoxazole core has been present in drugs such as sulfamethoxazole [13] contains antibiotic properties, muscimol [14] used as a selective GABAA agonist, ibotenic acid [15] that acts as a neurotoxin, parecoxib [16] shows COX-2 inhibitory properties, and leflunomide [17] behaves as an immunosuppressant agent (Figure 1).…”