Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks

Abstract

Abstract:Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine either in animal or epidemiologic studies. Theophylline and theobromine are other relevant methylxanthines also commonly available in the aforementioned sources. There are many disseminated myths about methylxanthines but there is increased scientific knowledge to discuss all the controversy and promise shown by these intriguing phytochemicals. In fact, many beneficial physiologic outcomes have been suggested for methylxanthines in areas as important and diverse as neurodegenerative and respiratory diseases, diabetes or cancer. However, there have always been toxicity concerns with methylxanthine (over)consumption and pharmacologic applications. Herein, we explore the structure-bioactivity relationships to bring light those enumerated effects. The potential shown by methylxanthines in such a wide range of conditions should substantiate many other scientific endeavors that may highlight their adequacy as adjuvant therapy agents and may contribute to the advent of functional foods. Newly designed targeted molecules based on methylxanthine structure may originate more specific and effective outcomes.

Zebrafish Embryo as an In Vivo Model for Behavioral and Pharmacological Characterization of Methylxanthine Drugs

“…Methylxanthines increases cAMP by inhibiting the phosphodiesterase enzymes (PDEs), however not all the methylxanthines act by this way. The increase in cyclic AMP also depends on the dose of the drugs used and their potency [2,6]. In our study, some drugs such as IBMX, caffeine, theophylline and pentoxifylline showed a significant increase in cyclic AMP in zebrafish embryos.…”

“…They are heterocyclic organic compounds consisting of pyrimidinedione and imidazole rings coupled with each other [1]. Methylxanthines are phytochemicals found in plants such as coffee, tea, mate, kola nuts and cacao beans [2]. Thus far, seven natural methylxanthines have been identified: aminophylline, caffeine, IBMX, paraxanthine, pentoxifylline, theobromine and theophylline [3].…”

“…Thus far, seven natural methylxanthines have been identified: aminophylline, caffeine, IBMX, paraxanthine, pentoxifylline, theobromine and theophylline [3]. Plants containing methylxanthines are often used to produce beverages such as coffee, tea, cacao, tejate and several other methylxanthine containing foods, which have been consumed on a daily basis [2]. In particular, caffeine forms a part of very popular and widely consumed soft drinks and energy drinks [4].…”

“…However, the use of methylxanthines is not only limited to beverages. Indeed, they are also being used for other major pharmacological effects [2,6,7]. …”

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…(Liu et al , 2014; Liu et al , 2013). Molecular SARs have been extensively and successfully used in the field of drug discovery and development (Akhtar et al , 2016; Cordomi et al , 2016; Monteiro et al , 2016; Putz et al , 2016; Sharma et al , 2016). Likewise the ultimate goal of developing nano-SARs is to enable prediction of toxicity based on ENM intrinsic physicochemical properties and thus enable safer by design development of commercial ENMs.…”