New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity
2023
Authors:
Bangay, GabrielleIsca, Vera
Domínguez-Martín, Eva María
Santos, Daniel J.V.A.
Díaz-Lanza, Ana María
Saraiva, Lucília
Afonso, Carlos A.M.
Jovanović, Mirna
Pešić, Milica
Rijo, Patricia
Document Type:
Conference object (Published version)
,
© 2023. Thieme
Metadata
Show full item recordAbstract:
Multidrug resistant (MDR) cancer cases continue to increase, such that the search for novel and more effective anti-cancer therapeutics is of high priority. In some MDR cancers, the overexpression of membrane transport proteins, like P-glycoprotein (P-gp), continues to be a major impediment to successful therapy. Plectranthus genus (Lamiaceae), known for their medicinal and therapeutic properties, is a well-known source of bioactive diterpenoids, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7- dehydroroyleanone (DeRoy). Based on in silico molecular docking studies, a small library of semi-synthetic derivates was prepared. The antitumoural activity of the compounds was assessed in resistant human cancer cell lines NCI-H460/R and DLD1-TxR. Cell viability was assessed using MTT assay and cell death induction by Annexin V/PI. Overall, it was demonstrated that three of the abietane diterpenoid analogues induced P-gp inhibition in MDR cancer cell lines, presenting novel selective compounds for the possible treatment of lung and colon cancer. Moreover, Roy and DeRoy nano-formulations were successfully prepared. DeRoy hybrid nanoparticles significantly increased the efficacy of DeRoy in NCI-H460 and NCI- H460/R. Roy, conjugated with oleic acid afforded self-assembly nanoparticles, to improve aqueous solubility and bioavailability of Roy. This new nano formulation did not decrease cell viability of Vero-E6 cells when compared to Roy with potential as a pro-drug delivery system. Currently, top hit derivatives are being prepared into nano-formulations for prospective pharmaceutical use as P-gp modulators.
Keywords:
royleanone; Plectranthus spp.; P-gpFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland. Stuttgart, Germany: Georg Thieme Verlag KG; 2023. p. 1424. (Planta Medica; Vol. 89; No. 14).