Background: Chalcones substituted by methoxyl groups have presented a broad spectrum
of bioactivities, including antifungal, antibacterial and antiproliferative effects. However, a
clear and unambiguous investigation about the relevance of this substituent on the chalcone
framework has not been described.
Objective: The purpose of this work is to assess the antibacterial, antifungal and antiproliferative
activities of the two series of seventeen synthesized regioisomeric methoxychalcones. Series I and
II were constituted by chalcones substituted by methoxyl groups on rings A (5–12) and B (13–21),
respectively. In addition, the library of methoxychalcones was submitted to in silico drug-likeness
and pharmacokinetics properties predictions.
Methods: Methoxychalcones were synthesized and their structures were confirmed by NMR spectral
data analyses. Evaluations of antimicrobial activity were performed against five species of
Candida, two Gram-negative and five Gram-positive species. For antiproliferative activity,
methoxychalcones were evaluated against four human tumorigenic cell lines, as well as human
non-tumorigenic keratinocytes. Drug-likeness and pharmacokinetics properties were predicted using
Molinspiration and PreADMET toolkits.
Results: In general, chalcones of series I are the most potent antifungal, antibacterial and antiproliferative
agents. 3’, 4’, 5’-Trimethoxychalcone (12) demonstrated potent antifungal activity
against Candida krusei (MIC = 3.9 μg/mL), eight times more potent than fluconazole (reference
antifungal drug). 3’-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8
μg/mL). 2’,5’-Dimethoxychalcone (9) displayed potent antiproliferative effect against C-33A
(cervix), A-431 (skin) and MCF-7 (breast), with IC50 values ranging from 7.7 to 9.2 μM. Its potency
was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values
ranging from 10.4 to 19.0 μM.
Conclusion: Our studies corroborated the relevance of methoxychalcones as antifungal, antibacterial
and antiproliferative agents. In addition, we elucidated influence of the position and number of
methoxyl groups toward bioactivity. In silico predictions indicated good drug-likeness and pharmacokinetics
properties to the library of methoxychalcones.