Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review
2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitatin...
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2025-01-01
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| author | Mohammad Aidiel Maisarah Abdul Mutalib Rajesh Ramasamy Nik Nasihah Nik Ramli Shirley Gee Hoon Tang Siti Hajar Adam |
| author_facet | Mohammad Aidiel Maisarah Abdul Mutalib Rajesh Ramasamy Nik Nasihah Nik Ramli Shirley Gee Hoon Tang Siti Hajar Adam |
| author_sort | Mohammad Aidiel |
| collection | DOAJ |
| description | 2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand–protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer. While lipophilicity is crucial for drug efficacy, the excessive lipophilic effects in flavonoids can reduce water solubility and hinder drug transport to target sites. Recent in vitro studies suggest that the incorporation of polar hydroxyl groups which can form hydrogen bonds and stabilize free radicals may help overcome the challenges associated with methoxy groups while maintaining their essential lipophilic properties. Naturally coexisting with methoxyflavones, this review explores the synergistic role of hydroxy and methoxy moieties through hydrogen bonding capacity in maximizing cytotoxicity against cancer cell lines. The physicochemical analysis revealed the potential intramolecular interaction and favorable electron delocalization region between both moieties to improve cytotoxicity levels. Together, the analysis provides a useful strategy for the structure–activity relationship (SAR) of flavonoid analogs in distinct protein markers, suggesting optimal functional group positioning to achieve balanced lipophilicity, effective hydrogen bonding, and simultaneously minimized steric hindrance in targeting specific cancer cell types. |
| format | Article |
| id | doaj-art-1cbb41fca1a54c02b6227438fc4af308 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-1cbb41fca1a54c02b6227438fc4af3082025-01-24T13:43:42ZengMDPI AGMolecules1420-30492025-01-0130234610.3390/molecules30020346Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A ReviewMohammad Aidiel0Maisarah Abdul Mutalib1Rajesh Ramasamy2Nik Nasihah Nik Ramli3Shirley Gee Hoon Tang4Siti Hajar Adam5School of Graduate Studies, Management & Science University, University Drive, Off Persiaran Olahraga, Section 13, Shah Alam 40100, MalaysiaSchool of Graduate Studies, Management & Science University, University Drive, Off Persiaran Olahraga, Section 13, Shah Alam 40100, MalaysiaDepartment of Pathology, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang 43400, MalaysiaSchool of Graduate Studies, Management & Science University, University Drive, Off Persiaran Olahraga, Section 13, Shah Alam 40100, MalaysiaCenter for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, MalaysiaPreclinical Department, Faculty of Medicine & Defence Health, Universiti Pertahanan Nasional Malaysia, Kuala Lumpur 57000, Malaysia2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand–protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer. While lipophilicity is crucial for drug efficacy, the excessive lipophilic effects in flavonoids can reduce water solubility and hinder drug transport to target sites. Recent in vitro studies suggest that the incorporation of polar hydroxyl groups which can form hydrogen bonds and stabilize free radicals may help overcome the challenges associated with methoxy groups while maintaining their essential lipophilic properties. Naturally coexisting with methoxyflavones, this review explores the synergistic role of hydroxy and methoxy moieties through hydrogen bonding capacity in maximizing cytotoxicity against cancer cell lines. The physicochemical analysis revealed the potential intramolecular interaction and favorable electron delocalization region between both moieties to improve cytotoxicity levels. Together, the analysis provides a useful strategy for the structure–activity relationship (SAR) of flavonoid analogs in distinct protein markers, suggesting optimal functional group positioning to achieve balanced lipophilicity, effective hydrogen bonding, and simultaneously minimized steric hindrance in targeting specific cancer cell types.https://www.mdpi.com/1420-3049/30/2/346medicinal plantsmethoxyflavonesphysicochemical propertiesstructural-activity relationshipanticancer mechanisms |
| spellingShingle | Mohammad Aidiel Maisarah Abdul Mutalib Rajesh Ramasamy Nik Nasihah Nik Ramli Shirley Gee Hoon Tang Siti Hajar Adam Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review Molecules medicinal plants methoxyflavones physicochemical properties structural-activity relationship anticancer mechanisms |
| title | Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review |
| title_full | Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review |
| title_fullStr | Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review |
| title_full_unstemmed | Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review |
| title_short | Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review |
| title_sort | mechanistic insights into the anticancer potential of methoxyflavones analogs a review |
| topic | medicinal plants methoxyflavones physicochemical properties structural-activity relationship anticancer mechanisms |
| url | https://www.mdpi.com/1420-3049/30/2/346 |
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