7/31/2019 Poster IJUP

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Prenylated Xanthonic Derivatives: Optimization of synthetic

methodologies and evaluation of physicochemical and biological

properties

J. Almeida1

, R. Castanheiro1,2

, M. Lcio3

, S. Reis3

, M. Pinto1,2

1Centro de Qumica Medicinal da Universidade do Porto (CEQUIMED-UP), Portugal.2Laboratrio de Qumica Orgnica e Farmacutica,Departamento de Cincias Qumicas, Faculdade de Farmcia, Universidade do Porto, Portugal.

3REQUIMTE, Departamento de Cincias Qumicas, Faculdade de Farmcia, Universidade do Porto, Portugal.

Results and

Discussion

Xanthone derivatives, namely prenylated xanthones (PXs) have been found to exhibit interesting activities such as anti-inflammatory,

antibacterial, antioxidant and antitumor [1,2]. The presence of prenyl groups becomes an important structural factor taking into account

the influence on the physicochemical properties, including lipophilicity, and the overall stereochemistry of the molecule, which may

create additional interactions with biological targets [1,2]. Therefore, PXs can represent excellent models for the development of new

and more effective drugs, being the introduction of prenyl groups in scaffold of "hit" compounds one of the strategies used in our

research group (CEQUIMED-UP) [3].

Classic Synthesis Non-ClassicSynthesis

Prenyl Bromide

K2CO3, Acetone

MW

X1 PX2 PX3

Green Chemistry

Micro-wave assisted

organic synthesis (MAOS)

Days and hours to minutes and seconds [4]

Heterogeneous

catalysis

Faster, cheaper, greener

Synthesis by Reflux

Biological Activity

Xanthone X1 PX2 PX3

Yield 4%

46%

1%

Physicochemical properties

Long reaction time

Inferior Yield

Its intended to determine the Log P and Pka of the

synthesized xanthones

Log P: determines distribution of a

drug between the aqueous

and the lipid environments[6]

Pka: measures the equilibrium

between unionized and ionized

drug[6]

8 hour (classic)

vs. 60 min

(MAOS)

[4]

Salicylic Acid

The 'A' in ADMET

Anti-inflamatory[7]

Anti-tumoractivity

AnalgesicAnti-piretic

Anti-oxidant

Classic MAOS

ee radical scavengers

3 hour (classic) vs.

40 min (MAOS)

K10 Clay

Cheap Non-toxicRecyclabe

ZnCl2 ,POCl3

MW

methilfluoroglucinol

events and repairs cell damage

Pinto, M., et al., (2005), Curr. Med. Chem., 12, 2517-2538.

Pinto, M. and Castanheiro, R., (2009) Natural Prenylated Xanthones: Chemistry and Biological Activities in Natural Products: Chemistry, Biochemistry and Pharmacology, Ed. Brahmachari, G., Narosa Publishing House PVT. LTD., Nova Deli, India, Ch. 17, pp.520-676.

Pinto, M. and Castanheiro, R. (2009), Curr. Org. Chem., 13(12), 1215-1240.

Kappe, C. O. And Dallinger, D. (2006). Nat. Rev Drug Discovery. 5, 51-63

Nagendrappa, G., Resonance, 2002, 64-77

vdeef, A. (2001) Physicochemucal profiling (solubility, permeability and charge state). Current Topics in Medicinal Chesmistry. 4, 277-351

Brune, B. H. K. (2002)."Cyclooxygenase: 210Years Later.The Journal Of Pharmacology And Experimental Therapeutics(300): 367-375.

[5]

Higher temperatures