| Full text | |
| Author(s): |
Marques, Beatriz C.
[1]
;
Santos, Mariana B.
[1]
;
Anselmo, Daiane B.
[1]
;
Monteiro, Diego A.
[2]
;
Gomes, Eleni
[2]
;
Saiki, Marilia F. C.
[2]
;
Rahal, Paula
[2]
;
Rosalen, Pedro L.
[3]
;
Sardi, Janaina C. O.
[3]
;
Regasini, Luis O.
[1]
Total Authors: 10
|
| Affiliation: | [1] Sao Paulo State Univ Unesp, Inst Biosci Humanities & Exact Sci, Dept Chem & Environm Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Sao Paulo State Univ Unesp, Inst Biosci Humanities & Exact Sci, Dept Biol, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[3] Univ Campinas Unicamp, Piracicaba Dent Sch, Dept Physiol Sci, BR-13083970 Piracicaba, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Medicinal Chemistry; v. 16, n. 7, p. 881-891, 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
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 cbalcones 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 mu g/mL), eight times more potent than fluconazole (reference antifungal drug). 3'-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8 mu g/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 mu M. Its potency was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values ranging from 10.4 to 19.0 mu M. 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. (AU) | |
| FAPESP's process: | 14/18330-0 - Synthesis and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors |
| Grantee: | Luis Octávio Regasini |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/09245-7 - Investigation of chalcones against Staphylococcus aureus MSSA and MRSA: evaluation of antibacterial, antibiofilm, anti-adsion activity and toxicity on Galleria mellonella |
| Grantee: | Beatriz de Carvalho Marques |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/18577-5 - Preparation and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors: methoxychalcones |
| Grantee: | Beatriz de Carvalho Marques |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules |
| Grantee: | Raghuvir Krishnaswamy Arni |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 18/15083-2 - Synthesis and biological evaluation of isobavachalcone (IBC) and analogs as potential agents against tuberculosis |
| Grantee: | Luis Octávio Regasini |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/08084-7 - Preparation and Biological Evaluation of Curcumin-Cinnamaldehyde Hybrids as Bacterial Cell Division Inhibitors: Methoxychalcones (Part 2) |
| Grantee: | Beatriz de Carvalho Marques |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 14/50926-0 - INCT 2014: biodiversity and natural products |
| Grantee: | Vanderlan da Silva Bolzani |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |