Design, synthesis, andIn vitroantituberculosis activity of 2(5H)-Furanone derivatives

Abstract

A series of 2(5H)-furanone-based compounds were synthesized from commercially available mucohalic acids. From the first-generation compounds, three showed inhibitory activity (10 mg/mL) of at least 35% against Mycobacterium smegmatis mc 2 155 growth (Bioscreen C system). In screening the active first-generation compounds for growth inhibition against Mycobacterium tuberculosis H37Rv, the most active compound was identified with a minimum inhibitory concentration (MIC 99 ) of 8.07 mg/mL (15.8 mM) using BACTEC 460 system. No cross-resistance was observed with some current first-line anti-TB drugs, since it similarly inhibited the growth of multidrug resistant (MDR) clinical isolates. The compound showed a good selectivity for mycobacteria since it did not inhibit the growth of selected Gram-positive and Gram-negative bacteria. It also showed synergistic activity with rifampicin (RIF) and additive activity with isoniazid (INH) and ethambutol (EMB). Additional time-kill studies showed that the compound is bacteriostatic to mycobacteria, but cytotoxic to the Chinese Additional Supporting Information may be found in the online version of this article. 612 IUBMB LifeHamster Ovarian (CHO) cell line. From a second generation library, two compounds showed improved anti-TB activity against M. tuberculosis H37Rv and decreased CHO cell cytotoxicity. The compounds exhibited MIC values of 2.62 mg/mL (5.6 mM) and 3.07 mg/mL (5.6 mM) respectively. The improved cytotoxicity against CHO cell line of the two compounds ranged from IC 50 5 38.24 mg/mL to IC 50 5 45.58 mg/mL when compared to the most active first-generation compound (IC 50 5 1.82 mg/mL). The two second generation leads with selectivity indices (SI) of 14.64 and 14.85 respectively, warrant further development as anti-TB drug candidates. V C 2016 IUBMB Life, 68(8):612-620, 2016

Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells

“…Regarding the compound structure, ZB5-1 has a furanone ring system. Also known as butyrolactone or butanolide, ZB5-1 is a widely recognized component of natural products, exhibiting an extensive spectrum of pharmacological activities [ 45 ]. Moreover, a quantitative structure-activity relationship (QSAR) analysis assessed that furanone derivatives would be a potential inhibitor of COX-2 [ 46 ].…”

The Current Status of O‐Heterocycles: A Synthetic and Medicinal Overview

“…Furthermore, they selected six structures, which weree valuated in the HCV sub-genomic replicon assay,a nd of these six, the best hit, compound 30 (Figure 7), was found to inhibitt he HCV replicon replication in the low micromolar range. [76] In 2015, Akhter et al identified quinoline-substituted furanone derivatives as selective falcipain-2 inhibitors and evaluated their antimalarialp otential. [74] In 2016, Khokra et al prepared al ibrary of 24 quinolinebased butenolides (furanones) and their nitrogen analogues.…”

“…From the second series, two compounds were reported to possess improved antitubercular activity against M. tuberculosis H37Rv. [76] In 2015, Akhter et al identified quinoline-substituted furanone derivatives as selective falcipain-2 inhibitors and evaluated their antimalarialp otential. Mosto ft he synthesised compoundsw ere reportedt ob es ignificantly potent with their activity being less than 5 mgmL À1 .T heir preliminary structure-activity relationship study suggested that increasing the electropositive character increased the antimalarial activity.I nt his work, Akhter et al hypothesised falcipain-2 as ap otential targetfor their compounds and hence,also performed molecular docking studies of the compounds with falcipain-2, which revealed vital interactions and theirb inding conformation.…”

Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5H)-Furanone Derivative against Staphylococcus aureus

“…These compounds were originally described as a natural tool of red algae Delisea pulchra , repressing its biofouling [6,7]. It has been shown that various furanones can either be produced naturally by a variety of microorganisms and plants or synthesized chemically [8,9,10]. In cells, furanones participate in intra- and inter-species signaling and communication, and act as attractants, pheromones, and antimicrobials [11].…”