Mini Reviews in Medicinal Chemistry - Volume 15, Issue 12, 2015

Vitamin D (VD) deficiency has re-emerged, after more than hundred years, as a public health problem worldwide. Asthma and allergic disorders constitute another major public health problem with studies having recorded increasing prevalences worldwide since the decade of the 60s. Most of the available experimental and epidemiologic evidence point towards a causal association between low levels of VD and the development of asthma and allergic disorders, and imply a role of VD deficiency on the currently high prevalences of asthma and allergic diseases. The proposed, but still largely hypothetical, underlying mechanism is that VD affects the programming of the fetus and it also has a central modulating role in immune functions involved in asthma and allergic disorders. However, the evidence is not yet clear, since there are studies which support that VD supplementation during pregnancy may promote the development of asthma and allergic disorders. More researches, and especially randomized clinical trials, are required in order to draw safe conclusions and define the role of VD in the prevention or even therapy of asthma and allergic disorders.

Vitamin D has been increasingly recognized as being involved in a wide spectrum of biological actions, including significant immunomodulatory effects. The cystic fibrosis (CF) airways are characterized by dysregulated and disproportionately increased, in relation to the underlying bacterial stimuli, inflammatory responses. Vitamin D downregulates pro-inflammatory cytokines and chemokines that promote tissue destruction, and which are abundant in CF lungs. However, despite mounting evidence for a pathophysiological role of Vitamin D in CF airways inflammation, there are only a few clinical reports supporting a relevance of Vitamin D insufficiency with CF airways damage, and so it is early to assign an indisputable causal role to Vitamin D. The present review will examine the current literature regarding the association of Vitamin D status with CF lung disease, and comment on the therapeutic implications accruing from these relations.

Inasmuch as many infants develop allergic symptoms early in infancy, and exposure to allergens may be important in the development of food allergies, there is great interest in maternal dietary strategies during pregnancy and lactation that may prevent food allergies, and thus reduce the burden of disease. Vitamin D levels are known to be associated with atopic disease development in early infancy; however, existing data are controversial. The aim of this review was to investigate any possible effect of vitamin D on the onset of neonatal allergy via breast feeding.

The crystal structures of the D3 dopamine receptor and several other G-protein coupled receptors (GPCRs) were published in recent times. Those 3D structures are used by us and other scientists as a template for the homology modeling and ligand docking analysis of related GPCRs. Our main scientific interest lies in the field of pharmacologically active N-arylpiperazines that exhibit antipsychotic and/or antidepressant properties, and as such are dopaminergic and serotonergic receptor ligands. In this short review article we are presenting synthesis and biological data on the new N-arylpipereazine as well our results on molecular modeling of the interactions of those N-arylpiperazines with the model of D2 dopamine receptors. To obtain that model the crystal structure of the D3 dopamine receptor was used. Our results show that the N-arylpiperazines binding site consists of two pockets: one is the orthosteric binding site where the N-arylpiperazine part of the ligand is docked and the second is a non-canonical accessory binding site for N-arylpipereazine that is formed by a second extracellular loop (ecl2) of the receptor. Until now, the structure of this receptor region was unresolved in crystal structure analyses of the D3 dopamine receptor. To get a more complete picture of the ligand - receptor interaction, DFT quantum mechanical calculations on N-arylpiperazine were performed and the obtained models were used to examine those interactions.

A wide range of health benefits have been attributed to wheatgrass, the young grass of the common wheat plant Triticum aestivum. Its components include chlorophyll, flavonoids, and vitamins C and E. Forms of wheatgrass include fresh juice, frozen juice, tablets, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Laboratory in vitro studies, mostly using the fermented wheat germ extract, have demonstrated anti-cancer potential and have identified apoptosis as a possible mechanism. In animal experiments, wheatgrass demonstrated benefits in cancer prevention and as an adjunct to cancer treatment, as well as benefits to immunological activity and oxidative stress. Clinical trials show that wheatgrass may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects, as well as benefit rheumatoid arthritis, ulcerative colitis, hematological diseases, diabetes, obesity, and oxidative stress. However, all the trials were small and a number of methodological problems arose. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability. The popularity of wheatgrass continues to grow. Nevertheless, the advantages seen in the clinical trials need to be proved in larger studies before clinical recommendations for the public can be given.

With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against tumor. Recently, many agents from CHM have shown powerful anti-angiogenic activities against tumor. In this review, we discussed the anti-tumor angiogenic activities of 6 kinds of agents from CHM (sulfated polysaccharides/glycopeptides, flavonoids, artemisinin, arsenic trioxide, ginsenoside, and tanshinone). The underlying pharmacological mechanisms of cancer angiogenesis inhibition by these agents are also gradually shown to us. Sulfated polysaccharides/glycopeptides and flavonoids may have synergistic effects with targeted anti-angiogenic drugs mainly targeting VEGF pathway by inhibiting bFGF and HIF-1α pathway, respectively. It is interesting that artemisinin and arsenic trioxide, two famous natural products worldwide, also have antitumor activity at least in part via angiogenesis inhibition. In addition, some natural products that are widely used for patients with cancer, such as ginseng and danshen, act as double-edged swords for tumor angiogenesis. Our review is aimed at providing an understanding of anti-angiogenic compounds from CHM and we propose that these breakthrough findings may have important implications for targeted-angiogenesis therapy and modernization of CHM.

Epilepsy is a serious brain condition characterized by recurring seizures. It affects millions of people across the globe. Much advancement in the past has improved the understanding of the underlying pathophysiology and risk factors for epilepsy. These advances have led to the development of both new terminologies and classification as well as treatment strategies for the disease. Despite the fact that various antiepileptic drugs have been developed in past decades, major part of affected population remains either resistant or refractory to the currently available therapy. Also, none of these anticonvulsant agents are devoid of serious side effect. Therefore, constant efforts are being made to develop antiepileptic drugs with improved efficacy and better pharmacokinetic and safety profile. The new structural classes which are being developed broadly amides, amino acids and a number of heterocyclic agents like oxadiazoles, benzimidazoles, benzothazoles, pyrazoles, indoles and benzothaizoles etc. These new compounds have potential for identification of novel targets and drug development. This review makes a note of these issues and describes recent developments in antiepileptic drug discovery.