Mini Reviews in Medicinal Chemistry - Volume 9, Issue 1, 2009

This paper is a general overview that contributes for the knowledge systematization concerning the characteristics of the acne in the adult, its prevalence, causes, diagnosis, classification and drugs available for treatment. The reference therapy is the combination between topical retinoids and oral antibiotics. Oral isotretinoin is still the only available therapy that may modify the different acne physiopathologic factors and therefore it is the standard treatment for severe acne. The importance of the acne treatment in the adult should be enhanced as it can also lead to symptoms of serious depression and anxiety.

Availability of selective pharmacological tools enabled a great advance of our knowledge of cannabinoid receptor 2 (CB2) role in pathophysiology. In particular CB2 emerged as an interesting target for chronic pain treatment as demonstrated by several studies on inflammatory and neuropathic preclinal pain models. The mechanisms at the basis of CB2-mediated analgesia are still controversial but data are pointing out in two main directions: an effect on inflammatory cells and/or an action on nociceptors and spinal cord relay centers. In this review will be described the second messenger pathways activated by CB2 agonists, the data underpinning the analgesic profile of CB2 selective agonists and the mechanisms invoked to explain their analgesic action. Finally the ongoing clinical trials and the potential issues for the development of a CB2 agonist drug will be examined.

A number of study have suggested a relationship between Helicobacter pylori infection and oxidative stress in the gastric epithelium. The oxidant- induced changes in zinc, iron, and vitamin C increase susceptibility to oxidative injury. Understanding of pathophysiologic mechanisms may provide new therapeutic strategies in treatment of oxidative injury of mucosa.

Epidemiological evidence suggests that flavonoids may play an important role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. Flavonoids are also common constituents of plants used in traditional medicine to treat a wide range of diseases. The purpose of this article is to summarize the distribution and biological activities of one of the most common flavonoids: luteolin. This flavonoid and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta. Dietary sources of luteolin include, for instance, carrots, peppers, celery, olive oil, peppermint, thyme, rosemary and oregano. Preclinical studies have shown that this flavone possesses a variety of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The ability of luteolin to inhibit angiogenesis, to induce apoptosis, to prevent carcinogenesis in animal models, to reduce tumor growth in vivo and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid has cancer chemopreventive and chemotherapeutic potential. Modulation of ROS levels, inhibition of topoisomerases I and II, reduction of NFkappaB and AP-1 activity, stabilization of p53, and inhibition of PI3K, STAT3, IGF1R and HER2 are possible mechanisms involved in the biological activities of luteolin.

NF-kappaB (NF-κB), the transcription factors of HIV-1, play an important role in triggering HIV transcription. The inhibition of NF-κB activation and their signaling pathway offers a potential anti-HIV therapy strategy. This review reports the mode of action of NF-κB in triggering HIV-1 transcription and the status of the inhibitors.

Deregulation of microRNA (miRNA) promotes carcinogenesis, as these molecules can act as oncogenes or tumor suppressor genes. Here we provide an overview of miRNA biology, discuss the most recent findings on miRNA and cancer development/progression, and report on how tumor-related miRNAs (oncomirs) are being used to develop novel cancer specific therapeutic approaches.

In this review article we have reported a series of hybrid compounds characterized by the presence of a α- halogenocryloyl alkylating moiety of low chemical reactivity, linked to known antitumor agents or their active moieties. Among them, brostallicin (PNU-166196), was selected for clinical development and is now undergoing Phase II studies in patients with advanced or metastatic soft tissue sarcoma.

In the armamentarium of calcium channel blockers appropriately functionalized 3,4-dihydropyrimidin-2(1H)- ones have received considerable attention in recent past owing to their structural similarity with 1,4-dihydropyridine based drugs. In this review, we highlight detailed investigations in the calcium channel blocking and other activities of this category of compounds as well as trace their genesis from 1,4-dihydropyridine based drugs.

Leishmaniasis, a group of tropical diseases caused by protozoan parasites of genus Leishmania, is a major health problem worldwide that affects millions of people especially in the developing nations. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness, but the growing incidence of their resistance has seriously hampered their use. In many cases the drugs employed for the treatment are toxic, marginally effective, given by injection and, compromised by the development of resistance. Therefore, the development of new mechanism based safe, effective and affordable chemotherapeutic agents to fight leishmaniasis would be an urgent priority research. The recent researches focused on natural products have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review briefly illustrates an account on current status of leishmaniasis, life cycle of parasites and biology, synergy of the disease with HIV, therapeutic options available to cure this disease and, highlights why natural products especially alkaloids as folk medicines are so important? Additionally, the outlines for the leishmanicidal activities of various alkaloids including indole, quinoline, isoquinoline, pyrimidine-β-carboline, steroidal and diterpene alkaloids from various plants as well as alkaloids from marine sources have been provided with their mechanistic studies.

Non-steroidal anti-inflammatory drugs (NSAIDs), commonly used for the treatment of chronic inflammatory diseases suffer from several undesired side effects, the most important being gastrointestinal (GI) irritation and ulceration. The prodrug designing is one of the several strategies used to overcome this drawback. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. In this paper, a review on the concept of prodrugs designing of NSAIDs to improve their efficacy and reduce the toxicity is being presented.