Design, synthesis, antimicrobial, and DNA gyrase inhibitory properties of fluoroquinolone–dichloroacetic acid hybrids

Abstract

A series of new fluoroquinolone conjugates 8a-g and 9a-f were synthesized via benzotriazole-mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR-QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties. K E Y W O R D S antibacterial, dichloroacetic acid, DNA gyrase, fluoroquinolone, hybrid conjugates F I G U R E 1 Examples of different class of antibiotics 250 | SELIEM Et aL.to microwave irradiation (Discover mode; run time: 60 s; Power Max-cooling mode). N-(Boc-aminoacyl)benzotriazoles 10a-g (Panda, Hall, et al., 2014; Panda, Naumov, et al., 2014) Compounds 10a-g were synthesized by irradiating an equimolar amount of Boc-protected amino acid with 1-(methylsulfonyl)-1H-benzo[d] [1,2,3]triazole (BtSO 2 Me) in the presence of 2.0 eq. of triethylamine for 2 min run time and 60 min hold time at 70°C and 50 W irradiation power. Completion of the reaction was monitored by TLC. After completion of the reaction, the mixture was quenched with water. The product obtained was extracted with ethyl acetate and then washed with a saturated solution of sodium carbonate and water to afford compound 10a-g. | General procedure for the preparation of

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

“…ADME (absorption, distribution, metabolism, and excretion) properties were determined by using a computational tool (Discovery Studio 2.5 software), [10] we believe these properties are important in addition to the pharmacological data. From the observed results (Supporting Information Table S4) it has been noticed that most of the tested agents show good aqueous solubility levels.…”

“…Our continuous research mission is to actively design and develop potential drug candidates for targeted diseases by this molecular hybridization approach. [ 8 , 9 , 10 , 11 , 12 , 13 ]…”

Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]

“…The cholinesterase properties observed were undertaken by CODESSA-Pro soware accessible for optimizing 2D-QSAR models. [39][40][41] This is useful for well understanding the bio-observations and identifying the parameters necessary for bio-potency. Three descriptor QSAR models were developed due Additionally, the correlations of the observed and predicted values "specially the high potent synthesized compounds" add good support for the attained models.…”

New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2

“…Our group has actively engaged in developing drug conjugates and hybrid conjugates by this approach. [21] , [22] , [23] , [24] , [25] , [26] …”