TY - JOUR
T1 - Targeting breast cancer cells with g4 pamam dendrimers and valproic acid derivative complexes
AU - Muñoz, Alberto M.
AU - Fragoso-Vázquez, Manuel J.
AU - Martel, Berenice P.
AU - Chávez-Blanco, Alma
AU - Dueñas-González, Alfonso
AU - R.garcía-Sánchez, José
AU - Bello, Martiniano
AU - Romero-Castro, Aurelio
AU - Correa-Basurto, José
N1 - Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Background: Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water. Objective: Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation. Methods: VPA derivatives were subjected to Docking and Molecular Dynamics (MD) simulations to evaluate their affinity on G4 PAMAM. Then, HPLC-UV/VIS,1H NMR, MALDI-TOF and atomic force microscopy were employed to establish the formation of the drug-G4 PAMAM complexes. Results: The docking results showed that the amide groups of VPA derivatives make polar interactions with G4 PAMAM, whereas MD simulations corroborated the stability of the complexes. HPLC UV/VIS experiments showed an increase in the drug water solubility which was found to be directly proportional to the amount of G4 PAMAM.1H NMR showed a disappearance of the proton amine group signals, correlating with docking results. MALDI-TOF and atomic force microscopy suggested the drug-G4 PAMAM dendrimer complexes formation. In vitro studies showed that G4 PAMAM has toxicity in the micromolar concentration in MDA-MB-231, MCF7, and 3T3-L1 cell lines. VPA CF-G4 PAMAM dendrimer complex showed anti-proliferative properties in the micromolar concentration in MCF-7 and 3T3-L1, and in the milimolar concentration in MDA-MB-231, whereas VPA MF-G4 PAMAM dendrimer complex didn’t show effects on the three cell lines employed. Conclusion: These results demonstrate that G4 PAMAM dendrimers are capableof transporting poorly water-soluble aryl-VPA derivate compounds to increase its cytotoxic activity against neoplastic cell lines.
AB - Background: Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water. Objective: Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation. Methods: VPA derivatives were subjected to Docking and Molecular Dynamics (MD) simulations to evaluate their affinity on G4 PAMAM. Then, HPLC-UV/VIS,1H NMR, MALDI-TOF and atomic force microscopy were employed to establish the formation of the drug-G4 PAMAM complexes. Results: The docking results showed that the amide groups of VPA derivatives make polar interactions with G4 PAMAM, whereas MD simulations corroborated the stability of the complexes. HPLC UV/VIS experiments showed an increase in the drug water solubility which was found to be directly proportional to the amount of G4 PAMAM.1H NMR showed a disappearance of the proton amine group signals, correlating with docking results. MALDI-TOF and atomic force microscopy suggested the drug-G4 PAMAM dendrimer complexes formation. In vitro studies showed that G4 PAMAM has toxicity in the micromolar concentration in MDA-MB-231, MCF7, and 3T3-L1 cell lines. VPA CF-G4 PAMAM dendrimer complex showed anti-proliferative properties in the micromolar concentration in MCF-7 and 3T3-L1, and in the milimolar concentration in MDA-MB-231, whereas VPA MF-G4 PAMAM dendrimer complex didn’t show effects on the three cell lines employed. Conclusion: These results demonstrate that G4 PAMAM dendrimers are capableof transporting poorly water-soluble aryl-VPA derivate compounds to increase its cytotoxic activity against neoplastic cell lines.
KW - Atomic force microscopy
KW - Breast cancer
KW - HDAC inhibitors
KW - HPLC
KW - Molecular docking
KW - Molecular dynamics
KW - PAMAM dendrimers
UR - http://www.scopus.com/inward/record.url?scp=85090650459&partnerID=8YFLogxK
U2 - 10.2174/1871520620666200423073812
DO - 10.2174/1871520620666200423073812
M3 - Artículo
C2 - 32324521
AN - SCOPUS:85090650459
SN - 1871-5206
VL - 20
SP - 1857
EP - 1872
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 15
ER -