Mini Reviews in Medicinal Chemistry - Volume 16, Issue 12, 2016

Both epidemiological and experimental data indicate that ionizing radiation (IR) may disrupt developmental processes leading to deleterious effects on brain functions. A central role of reactive oxygen (ROS) and nitrogen species (RNS), as important mediators in neurotoxicity and neuroprotection, has been demonstrated. Primary ionization events triggered by IR are amplified and propagated by mechanisms involving ROS and RNS, which activate several signaling pathways leading to final radiation effects. The immature and adult brain display clear differences in the way they respond to insults. Moreover, a great deal of attention is being focus on the limited antioxidant capacity and the particular lipid composition of cell membranes of the developing brain that render it more vulnerable to oxidative stress. The goal of this review is to summarize the current knowledge on the role of alterations in the balance between oxidative/nitrosative stress and antioxidant capacity in the pathways involved in cellular radiation response, with particular focus on the possible therapies proposed to limit radiation-induced effects in the brain.

Interferons are produced in vivo and are one of the prime components of natural defense system of animals. They are released by the viral infected cells and provide protection to the neighboring cells against viral infection. The cyto-protective property of the proteins ignited the thought of their pharmaceutical adaptation for therapeutic use against viral diseases in individuals in whom the interferons released naturally are not sufficient to combat the situation. Interferon supplements have been found to complement various antiviral drugs. Considering the efficacy of interferons in regulating angiogenesis and immunomodulation, they can be adapted for therapy of the killer diseases like cancer and AIDS. We have come ahead more than twenty five years after the approval of clinical use of interferon as drugs and are today really in a position to promise a disease free life to our present and next generation. Interferon therapy will be contributing a big share to the upcoming remedies for the new diseases and we are thus armed to fight back the deadly viral threats. Interferons have been modified [pegylated etc.] and have already been adapted to some extent in certain diseases and are in regular use in some. Thus interferons if modified as per need and used in combination with either antiviral drugs, antibiotics, antioxidants may strengthen our defense system effectively to bring about a strong protection against wide range of diseases.

Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma.

Epidemiological evidences establish sulforaphane (SFN), a hormetic dietary isothiocyanate to be a promising chemopreventive, anti-inflammatory and anti-cancer agent. Beyond a concentration threshold SFN exerts pro-death activities (cell cycle arrest, epigenetic modifications and apoptosis) and below the threshold it either promotes prosurvival autophagy or remains latent. There is a significant lacuna in understanding the underpinning dynamic molecular networks that alternate the pharmacological responses with respect to the intracellular concentration and exposure time that renders SFN to be a characteristic hormetic molecule (display characteristic biphasic dose response curve). Unraveling this multi-targeted SFN triggered molecular interplay between apoptosis and pro-survival autophagy may have great therapeutic implications. From the available literature, here we present a review that illustrates the existence of a hormetic window and briefly discussed its role in the spectrum of activity of SFN in different pathological conditions (cancer and immune-mediated diseases). Further, we hypothesize a hormetic signaling event on how SFN triggers mutually exclusive molecular pathways such as cell survival or death signals depending on its pathophysiological environment, exposure time and in vitro working concentrations. By better understanding these altered events and underpinning mechanisms in different combinations such as concentrations and time a proper therapeutic can be designed.

Pyridazinone and its derivatives have various ranges of biological and pharmacological activities including anti-inflammatory, antifeedant, anticonvulsant, antidiabetic, herbicidal, antihypertensive, antiplatelet, antifungal, antibacterial, anticancer and antiviral activities. Pyridazinone magic moiety has allowed the generation of a huge number of structurally different derivatives. Most of the pyridazinone derivatives are derived from substitution of the pyridazinone oxygen, nitrogen and C4/C5/C6 carbon positions. Pyridazinone can be used for the synthesis of a large variety of heterocyclic compounds and as intermediate for a broad spectrum of drug synthesis. Constant use of non-steroidal anti-inflammatory drugs is often accompanied by side effects such as bleeding, nephrotoxicity and gastrointestinal lesions. To minimise these side effects some of the pyridazinone derivatives are synthesised with an improved gastrointestinal tract and renal safety profile linked to other non-steroidal anti-inflammatory drugs. In this review, we have discussed the pyridazinone nucleus which serves as an important therapeutic agent in the field of nonsteroidal anti-inflammatory drugs. This nucleus has a wide spectrum in bioorganic and medicinal chemistry and application in drug discovery.

Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products.