Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives

Feng, Lian‐Shun; Maddox, Marcus M.; Alam, Zahidul; Tsutsumi, Lissa S.; Narula, Gagandeep; Bruhn, David F.; Wu, Xiaoqian; Sandhaus, Shayna; Lee, Robin B.; Simmons, Charles J.; Tse-Dinh, Yuk Ching; Hurdle, Julian G.; Lee, Richard; Sun, Dianqing

doi:10.1021/jm500853v

Cited by 94 publications

(60 citation statements)

References 77 publications

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“…aureus , compared than the reference drug chloramphenicol (Khan, Asiri, & Elroby, ). Evaluation of the antibacterial activity of modified structures of olympicin A from Hypericum olympicum showed that ( E )‐3‐(2‐(allyloxy) phenyl)‐1‐(2,4,6‐trihydroxyphenyl)prop‐2‐en‐1‐one ( 148 ) had a good activity against MRSA with MIC value of 0.39 μg/ml (Feng et al, ). Between the synthetic tricyclic flavonoids, compounds 149 and 150 (1,3‐dithiolium derivative) showed good activity with MICs of 0.25 and 1 μg/ml against S .…”

Section: Synthetic Derivatives Of Flavonoidsmentioning

confidence: 99%

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

Farhadi

Khameneh

Iranshahi

et al. 2018

Phytotherapy Research

487

305

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Based on World Health Organization reports, resistance of bacteria to well-known antibiotics is a major global health challenge now and in the future. Different strategies have been proposed to tackle this problem including inhibition of multidrug resistance pumps and biofilm formation in bacteria and development of new antibiotics with novel mechanism of action. Flavonoids are a large class of natural compounds, have been extensively studied for their antibacterial activity, and more than 150 articles have been published on this topic since 2005. Over the past decade, some promising results were obtained with the antibacterial activity of flavonoids. In some cases, flavonoids (especially chalcones) showed up to sixfold stronger antibacterial activities than standard drugs in the market. Some synthetic derivatives of flavonoids also exhibited remarkable antibacterial activities with 20-to 80-fold more potent activity than the standard drug against multidrug-resistant Gram-negative and Gram-positive bacteria (including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). This review summarizes the ever changing information on antibacterial activity of flavonoids since 2005, with a special focus on the structure-activity relationship and mechanisms of actions of this broad class of natural compounds.

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Section: Synthetic Derivatives Of Flavonoidsmentioning

confidence: 99%

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

Farhadi

Khameneh

Iranshahi

et al. 2018

Phytotherapy Research

487

305

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“…In our ongoing efforts to discover new topoisomerase I inhibitors as antibacterial agents and to probe the topoisomerase I recognition [8, 9], we identified during high-throughput screening (HTS) assay development a compound NSC648059 ( 1 , Fig. 1) with low micromolar inhibitory activity (IC 50 = 0.8–2.0 µM) against Escherichia coli topoisomerase I.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as bacterial topoisomerase IA inhibitors

Zhang

Annamalai

et al. 2017

European Journal of Medicinal Chemistry

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New antibacterial agents with novel target and mechanism of action are urgently needed to combat problematic bacterial infections and mounting antibiotic resistances. Topoisomerase IA represents an attractive and underexplored antibacterial target, as such, there is a growing interest in developing selective and potent topoisomerase I inhibitors for antibacterial therapy. Based on our initial biological screening, fluoroquinophenoxazine 1 was discovered as a low micromolar inhibitor against E. coli topoisomerase IA. In the literature, fluoroquinophenoxazine analogs have been investigated as antibacterial and anticancer agents, however, their topoisomerase I inhibition was relatively underexplored and there is little structure-activity relationship (SAR) available. The good topoisomerase I inhibitory activity of 1 and the lack of SAR prompted us to design and synthesize a series of fluoroquinophenoxazine analogs to systematically evaluate the SAR and to probe the structural elements of the fluoroquinophenoxazine core toward topoisomerase I enzyme target recognition. In this study, a series of fluoroquinophenoxazine analogs was designed, synthesized, and evaluated as topoisomerase I inhibitors and antibacterial agents. Target-based assays revealed that the fluoroquinophenoxazine derivatives with 9-NH2 and/or 6-substituted amine functionalities generally exhibited good to excellent inhibitory activities against topoisomerase I with IC50s ranging from 0.24–3.9 µM. Notably, 11a bearing the 6-methylpiperazinyl and 9-amino motifs was identified as one of the most potent topoisomerase I inhibitors (IC50 = 0.48 µM), and showed broad spectrum antibacterial activity (MICs = 0.78–7.6 µM) against all the bacteria strains tested. Compound 11g with the 6-bipiperidinyl lipophilic side chain exhibited the most potent antituberculosis activity (MIC = 2.5 µM, SI = 9.8). In addition, CoMFA analysis was performed to investigate the 3D-QSAR of this class of fluoroquinophenoxazine derivatives. The constructed CoMFA model produced reasonable statistics (q2 = 0.688 and r2 = 0.806). The predictive power of the developed model was obtained using a test set of 7 compounds, giving a predictive correlation coefficient r2pred of 0.767. Collectively, these promising data demonstrated that fluoroquinophenoxazine derivatives have the potential to be developed as a new chemotype of potent topoisomerase IA inhibitors with antibacterial therapeutic potential.

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“…One such pharmacophoric unit is chromone which is recognized as a useful motif for the design of biologically relevant entities and is also prevalent in many natural products. [5][6][7][8][9][10] Spiro chromanones too are known to be bio-active molecules with activities ranging from anti-inammatory, anti-cancer, anti-bacterial and anti-fungal properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 8′,11′-dihydrospiro[cyclohexane-1,2′-oxepino[2,3-h] chromen]-4′(3′H)-ones with ring closing metathesis as a key step

Ashok

Sarasija

et al. 2018

RSC Adv.

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Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives

Cited by 94 publications

References 77 publications

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as bacterial topoisomerase IA inhibitors

Synthesis of 8′,11′-dihydrospiro[cyclohexane-1,2′-oxepino[2,3-h] chromen]-4′(3′H)-ones with ring closing metathesis as a key step

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