Synthesis of new symmetric cyclic and acyclic halocurcumin analogues typical precursors for hybridization
- PDF / 1,453,736 Bytes
- 17 Pages / 439.37 x 666.142 pts Page_size
- 67 Downloads / 135 Views
Synthesis of new symmetric cyclic and acyclic halocurcumin analogues typical precursors for hybridization Sawsan A. Noureddin1,2 · Reda M. El‑Shishtawy1,3 · Khalid O. Al‑Footy1 Received: 18 May 2020 / Accepted: 31 August 2020 © Springer Nature B.V. 2020
Abstract It is believed that the synthesis of hybrid molecules containing different biologically relevant moieties would furnish multifunctional drugs with the possible synergism of potential importance for the treatment of cancer, diabetic and Alzheimer diseases. It was envisioned that synthesizing different cyclic and acyclic halocurcumin intermediates would furnish key precursors for hybridization. Thus, starting from vanillin (I) as a naturally occurring compound, several O-haloalkyl derivatives (IIa, IIb and III) have been synthesized and characterized. These derivatives were subjected to Knoevenagel condensation reaction with deferent acyclic and cyclic ketones to afford the corresponding symmetric halocurcumin analogues (IV–VIII). The chemical structures of the newly synthesized curcumin intermediates were confirmed with spectroscopic techniques. These analogues, having primary halogen from both sides, are typical precursors of hybrid curcumin analogues. Graphic abstract
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116 4-020-04264-y) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article
13
Vol.:(0123456789)
S. A. Noureddin et al.
Fig. 1 Chemical structure of curcumin
Keywords O-alkylation · Knoevenagel condensation · Intermediates · Hybridization · Halocurcumin
Introduction Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) (Fig. 1) is an interesting yellow compound that has several chemical features due to its unique structure that possesses two phenyl rings (with o-methoxy and p-hydroxy groups) connecting via seven carbon linker with diketone groups [1]. The chemical structure of this compound is essential for its broad spectrum of biological and pharmacological activities and medicinal properties such as antioxidant, anti-inflammatory, anticancer, antiviral and anti-Alzheimer’s diseases effects [1–7]. Furthermore, it is characterized by its safety for oral administration [8]. Unfortunately, it is not used in medication to treat diseases due to its poor solubility and bioavailability [9]. Scientists tried to overcome this problem in several ways, such as to improve its solubility [10, 11], synthesis of curcumin nanoparticles [12] and combination with adjuvants [2, 13, 14]. Also, a vast number of curcumin derivatives and analogues, either symmetric or asymmetric with di- or monocarbonyl groups, were synthesized and evaluated for their biological activities [6–10, 15–18]. It was found that the type of substituents and the pattern of the bioactive molecule are crucial regarding the interesting biological activities [19]. Several structure activity relationship (SAR) studies indicated
Data Loading...
