In vitro and in vivo synergistic interaction of substituted chalcone derivatives with norfloxacin against methicillin resistant Staphylococcus aureus

Gaur, Rashmi; Gupta, Vivek Kumar; Pal, Anirban; Darokar, Mahendra P.; Bhakuni, R. S.; Kumar, Brijesh

doi:10.1039/c4ra10842f

Cited by 33 publications

(15 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43,61 Compounds 6a, 6c, 6d, and 6f, with LC 50 values of 8.03, 6.66, 9.09, and 10.80 mg L −1 , respectively, and LC 90 values of 11.9, 9.97, 13.58, and 18.21 mg L −1 , respectively, fall in this category. Analysis of structure-activity relationships has guided the synthesis of substituted chalcone derivatives to obtain molecules with other biological properties, such as antimicrobials, 62 compounds for immunodiagnosis of Parkinson's disease, 63 and antioxidants. 64 The presence of a free hydroxyl group in the aromatic ring of chalcones increases the A-ring lipophilicity 64 and is an important structural feature for the antimicrobial activity against methicillin-resistant Staphylococcus aureus.…”

Section: Discussionmentioning

confidence: 99%

Larvicidal activity of substituted chalcones against Aedes aegypti (Diptera: Culicidae) and non‐target organisms

Targanski

Sousa

Pádua

et al. 2020

Pest Management Science

View full text Add to dashboard Cite

BACKGROUND: The expansion of Aedes aegypti (Diptera: Culicidae) population has increased the number of cases of arboviruses, in part due to the inefficiency and toxicity of the chemical control methods available to control this vector. We synthesized 19 chalcone derivatives and examined their activity against Ae. aegypti larvae in order to select larvicidal compounds that are non-toxic to other organisms. RESULTS: Seven chalcone derivatives (3a, 3e, 3f, 6a, 6c, 6d, and 6f) had lethal concentrations of substituted chalcones capable of killing 50% (LC 50) values lower than 100 mg mL −1 at 24 h post-treatment, which is the dose that the World Health Organization recommends for the selection of promising larvicides. The type of substituent added to (E)-1,3-diphenylprop-2-en-1-one (3a) markedly affected the larvicidal activity. Addition of chlorine, bromine and methoxy groups to the aromatic rings reduced the larvicidal activity, while replacement of the Bring (phenyl) by a furan ring significantly increased the larvicidal activity. The furan-chalcone (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) killed Ae. aegypti larvae (LC 50 = 6.66 mg mL −1 ; LC 90 = 9.97 mg mL −1) more effectively than the non-substituted chalcone (3a) (LC 50 = 14.43 mg mL −1 ; LC 90 = 20.96 mg mL −1), and was not toxic to the insect Galleria mellonella, to the protozoan Tetrahymena pyriformis, and to the algae Chorella vulgaris. CONCLUSIONS: The substitution pattern of chalcones influenced their larvicidal activity. In the set of compounds tested, (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) was the most effective larvicide against Ae. aegypti, with no clear signs of toxicity to other animal models. Its mechanism of action and effectiveness under field conditions remain to be determined.

show abstract

Section: Discussionmentioning

confidence: 99%

Larvicidal activity of substituted chalcones against Aedes aegypti (Diptera: Culicidae) and non‐target organisms

Targanski

Sousa

Pádua

et al. 2020

Pest Management Science

View full text Add to dashboard Cite

show abstract

“…Alongside the modification of naringenin with O -alkyl chains, the incorporation of an oxime group was observed to significantly increase its biological activity. In many cases, the replacement of the carbonyl group with an oxime at the C-4 position resulted in higher antibacterial [ 20 ] and cytotoxic activities [ 21 ]. The modification of naringenin to its oxime enhanced its antitumor activity against rat pheochromocytoma (PC-12), human colon (HT-29) and breast (MCF-7) cancer cell lines [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity

et al. 2019

View full text Add to dashboard Cite

In our investigation, we concentrated on naringenin (NG)—a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel O-alkyl derivatives of naringenin (7a–11a, 13a, 17a) were obtained. Another chemical modification led to 9 oximes of O-alkyl naringenin derivatives (7b–13b, 16b–17b) that were never described before. The obtained compounds were evaluated for their potential antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The results were reported as the standard minimal inhibitory concentration (MIC) values and compared with naringenin and its known O-alkyl derivatives. Compounds 4a, 10a, 12a, 14a, 4b, 10b, 11b, and 14b were described with MIC of 25 µg/mL or lower. The strongest bacteriostatic activity was observed for 7-O-butylnaringenin (12a) against S. aureus (MIC = 6.25 µg/mL). Moreover, the antitumor effect of flavonoids was examined on human colon cancer cell line HT-29. Twenty-six compounds were characterized as possessing an antiproliferative activity stronger than that of naringenin. The replacement of the carbonyl group with an oxime moiety significantly increased the anticancer properties. The IC50 values below 5 µg/mL were demonstrated for four oxime derivatives (8b, 11b, 13b and 16b).

show abstract

“…The indole–chalcone hybrids 47a , b (MIC: 12.5–100 µM) showed a considerable activity against 10 MRSA clinical isolates, including MRSA ST‐1745, MRSA ST‐2071, MRSA ST‐2438, MRSA ST‐8029, MRSA ST‐5457, MRSA ST‐10342, MRSA ST‐10760, MRSA ST‐3151, and MRSA P‐6642, and the SAR demonstrated that the electron‐donating group on the phenyl ring increased the activity, whereas the electron‐withdrawing group decreased the activity. [ 79 ] Hybrid 47a (MIC: 12.5–50 µM), which was found to be 5‐ to 40‐fold more potent than the reference norfloxacin (MIC: 125–500 µM) against 10 MRSA clinical isolates, also exhibited a synergistic effect with norfloxacin, as the combination of this hybrid with norfloxacin led to a 2‐ to 16‐fold reduction in MIC values of norfloxacin against the tested MRSA isolates. The mechanistic study proved that hybrid 47a could exert the antibacterial activity through blocking multidrug‐resistant efflux pump.…”

Section: Indole Hybridsmentioning

confidence: 99%

“…[78] The indole-chalcone hybrids 47a,b (MIC: 12. and MRSA P-6642, and the SAR demonstrated that the electrondonating group on the phenyl ring increased the activity, whereas the electron-withdrawing group decreased the activity. [79] Hybrid 47a but also demonstrated a potential inhibitory activity (IC 50 : 355 and 24 nM) against MRSA PK. [80] The SAR revealed that 2-hydroxyl-5bromophenyl group was crucial for the high activity, and replacement of this fragment by the second indole moiety reduced the activity; the substituent at the C-6 position also had great influence on the activity, and the bromo group was beneficial for the activity.…”

Section: Indole Hybridsmentioning

confidence: 99%

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

Meng

Hou

Shang

et al. 2020

Archiv der Pharmazie

View full text Add to dashboard Cite

Methicillin‐resistant Staphylococcus aureus (MRSA), one of the major and most dangerous pathogens in humans, is a causative agent of severe pandemic of mainly skin and soft tissue and occasionally fatal infections. Therefore, it is imperative to develop potent and novel anti‐MRSA agents. Indole derivatives could act against diverse enzymes and receptors in bacteria, occupying a salient place in the development of novel antibacterial agents. Dimerization and hybridization are common strategies to discover new drugs, and a number of indole dimers and hybrids possess potential antibacterial activity against a panel of clinically important pathogens including MRSA. Accordingly, indole dimers and hybrids are privileged scaffolds for the discovery of novel anti‐MRSA agents. This review outlines the recent development of indole dimers and hybrids with a potential activity against MRSA, covering articles published between 2010 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective candidates.

show abstract

In vitro and in vivo synergistic interaction of substituted chalcone derivatives with norfloxacin against methicillin resistant Staphylococcus aureus

Abstract: The present investigation shows that certain substituted chalcone derivatives diminish the escalation of bacterial cellsviainhibiting bacterial efflux pump and exhibit a synergistic interaction with norfloxacin.

Cited by 33 publications

References 60 publications

Larvicidal activity of substituted chalcones against Aedes aegypti (Diptera: Culicidae) and non‐target organisms

Larvicidal activity of substituted chalcones against Aedes aegypti (Diptera: Culicidae) and non‐target organisms

Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

Contact Info

Product

Resources

About