Chapter 7 - Curcumin, a Multitarget Phytochemical: Challenges and Perspectives
Introduction
Curcumin or diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione, is a polyphenolic natural and the major constituent in the rhizome of the Curcuma longa Linn (Turmeric). Previous studies showed that there is a difference in the curcumin content among different lines of C. longa specie [1]. Commercial curcumin contains approximately 77 percent diferuloylmethane, 17 percent demethoxycurcumin, and 6 percent bisdemethoxycurcumin. It is an orange-yellow crystalline powder, practically insoluble in water and ether, but soluble in ethanol, dimethyl sulfoxide, and acetone.[2] Biological properties exhibited by curcumin include antifungal [3], anti-inflammatory [4], antioxidant [5], antiangiogenic [6], anti-HIV [7], neuroprotective [8], chemopreventive [9] and antitumor [10]. The therapeutic effects of curcumin are attributed to its action over a wide range of molecular targets [11]. Due to its excellent pharmacodynamic profile and remarkable lack of toxicity (no dose-limiting toxicity at doses up to 8 g/day in humans), curcumin proceeded to clinical trials [12]. However, curcumin possesses several limitations, such as chemical instability, poor aqueous solubility, low bioavailability, and fast metabolism under physiological conditions, thereby resulting in a rapid systemic elimination, which limits its application as a drug [13]. In this current chapter, we revised the main molecular features and potential medical applications of curcumin and exposed recent approaches to improve this molecule to be effectively applied in medical clinical practice.
Section snippets
Curcumin Molecular Features
Curcumin molecular structure is composed of a diferuloyl linked by a methane with a low molecular mass of 368.37 g/mol; its melting temperature is approximately 183°C. The two aryl rings containing orthomethoxy phenolic groups (OH) are symmetrically linked to a diketone moiety, as illustrated in Fig. 7.1. In silico profiling of curcumin determined an octanol-water partition coefficient of 2.3, the number of hydrogen-bond acceptors (O and N atoms) 6, the number of hydrogen-bond donors (OH and NH
Antitumor Activity
Among the various natural compounds tested for antitumor activity, curcumin stands out due to a large amount of data showing its promising effect on different tumor types, either in vitro and in vivo models, by acting in particular on tumor growth, apoptosis, and angiogenesis [23], [24]. Additionally, clinical studies have shown that curcumin can lead to the regression of premalignant lesions of some tumors, indicating its great potential as an antitumor agent [25], [26].
Among the various
Curcumin Antioxidant Activity
The body creates free radicals through the normal processes of metabolism. When the amount of free radicals exceeds the body's ability to eliminate or neutralize them, an oxidative imbalance occurs, named as oxidative stress. During the metabolism of aerobic organisms, a series of biochemical/physiological events lead to the formation of reactive oxygen species (ROS) [49], as superoxide anion (), hydroxyl radical (•OH), hypochlorous acid (HOCl), and peroxynitrite (ONOO−), playing an
Curcumin Anti-HIV
The study of the curcumin and curcuminoids compounds reveal that these molecules act against a variety of viruses, including human immunodeficiency virus (HIV), influenza, herpes simplex virus (HSV), hepatitis C virus (HCV), Human papillomavirus (HPV), Japanese encephalitis virus (JEV), and human T-lymphotropic virus type 1 (HTLV-I) [80]. The curcumin targets in HIV virus are HIV-1 and HIV-2 proteases, HIV integrase, nuclear factor-B activation [81], inhibition of p300/CREB-binding
Antifungal Activity
A large increase in immunocompromised patients in recent years, due to the advancement of therapy with immunosuppressants and the growing number patients with immunosuppressive diseases, has resulted in a sharp increase in the incidence of opportunistic infections, which mainly related to fungal infections. In such cases the infections caused by pathogens of the genera Candida, Cryptococcus and Aspergillus have been implicated as an important factor in cases of mortality [92].
Treatment for
Curcumin Analogs
The curcumin limitations, such as chemical instability, poor aqueous solubility, low bioavailability and fast metabolism under physiological conditions has been the subject of study via two main strategies: (a) synthesis of new curcumin analogs and (b) development of new delivery systems.
Several studies have described the synthesis of novel curcumin analogs based on the modification of functional groups contained in its structure (Fig. 7.1). Various substitutions in the functional regions are
Nanotechnological Approaches to Curcumin Delivery
Nanotechnology applied to drug delivery and targeting represents an efficient strategy to improve drug physicochemical properties, enhance drug efficacy and specificity, and reduce drug toxicity. Nanostructured carriers have several important advantages that can enhance drug properties, including: (i) improved solubility of hydrophobic drugs; (ii) increased drug bioavailability; (iii) improved drug stability under physiological conditions; (iv) surface characteristics that modulates the uptake
Concluding Remarks
Curcumin is a natural product with promising biological properties; therefore there is great interest in expanding the study of its antitumor and antioxidant effects. Several studies have demonstrated the safety of curcumin's use in vivo, an important aspect in relation to its potential pharmacological application.
Due to its chemical characteristics, various analogs of curcumin were synthesized and evaluated, yielding compounds with greater efficacy and an interesting strategy to enhance their
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