Mini Reviews in Medicinal Chemistry - Volume 14, Issue 3, 2014

Organophosphates are used as pesticides or misused as warfare nerve agents. Exposure to them can be fatal and death is usually caused by respiratory arrest. For almost six decades, pyridinium oximes represent a therapeutic tool used for the management of poisoning with organophosphorus (OP) compounds. However, these compounds possess several drawbacks. Firstly, they are inefficient in the restoration of brain acetylcholinesterase (AChE) activity due to a hard blood-brain barrier penetration. Secondly, there is no broad-spectrum AChE reactivator. Lastly, none of the oximes can reactivate “aged” AChE. In this context, uncharged reactivators represent a new hope in a way of increased bioavailability in the central compartment and better therapeutic management of the OP poisoning.

Despite the enormous advances in the development of new drugs, the efficacy of current antitumor therapies is still quite limited, most likely because of the high degree of cancer heterogeneity and cell signaling complexity. As a single drug does not necessarily eradicate the cancer, the use of drug combinations has been proposed, and numerous studies have already been conducted to examine the efficacy of this strategy. In the last decade, parthenolide, a plantderived sesquiterpene lactone, was extensively studied and its potential to inhibit cancer cell growth in vitro was well documented. More recently, antitumor effects exerted by parthenolide in combination with various drugs routinely used in cancer treatment have been investigated in several laboratories. In this article studies that are underway in an attempt to improve the anticancer efficacy of chemotherapies through combination strategies involving parthenolide are summarized.

The [1,4]benzodiazepine is an important class of heterocyclic compounds and clinically used for many ailments in humans. The [1,4]benzodiazepine has unique structure that mimics the peptide linkage. This interesting observation completely shifted the interest of medicinal chemist for [1,4]benzodiazepine from CNS acting drugs to anticancer agents. During last few decades, a large number of reports have appeared in the literature highlighting the anticancer activity of [1,4]benzodiazepines. Here, in this article, we have discussed the brief synthesis, origin of [1,4]benzodiazepines as anticancer agent, their mechanism of action and latest developments in this field. We have compiled the most important literature reports from last few decades till date.

Benign prostatic hyperplasia (BPH) is the noncancerous growth of the prostate gland resulting due to overproliferation of the stromal and glandular elements of the prostate and is associated with lower urinary tract symptoms. Natural products, containing inherently vast structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continue to play as protagonists for discovering new drugs. Phytotherapeutic products have been used traditionally in developing countries while the use of them as complementary alternative medicine is increasing rapidly in developed countries for the management of BPH. Although mono preparations (single plant only) are available, many industries manufacture combination products (plant extracts) in an attempt to provide enhanced efficacy to improve marketability, and to provide their own “unique” product that can be registered, because these products have no patent protection. The mechanism of action of the phytotherapeutic agents is not clearly understood as many in vitro experimental studies have demonstrated diverse spectrum of mechanisms. The main mechanisms of action that has received the greatest attention are anti-inflammatory, 5α-reductase inhibition, and more recently growth factor alteration. The current review covers all such studies and critiques the efficacy and value of such phytotherapeutic products and preparations available for the management of BPH.

Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β (Aβ) peptide in the brains of AD patients. Such a process is linked to the binding of metal ions (e.g., Cu, Fe and Zn) with Aβ. As a result, metal chelation could be used as a rational therapeutic pathway for the treatment of AD. In this review, we address some noteworthy advances on the utilization of metal chelators, such as native metallothioneins and synthetic compounds, as potential therapeutic agents for AD. In addition, the future design and utility of metal chelating drugs as well as the strategy pursued to transport metal chelators into the brain are highlighted. We believe that this contribution will be valuable for the design of metal-chelating drugs for AD treatment.

The 1, 4-dihydropyridines (DHPs), a class of drugs possess a wide variety of biological and pharmacological actions. It represents one of the most important groups of calcium-channel modulating agents and has experienced widespread use in the treatment of cardiovascular disease which includes antihypertensive, antianginal, vasodilator and cardiac depressants activities. It also shows antibacterial, anticancer, antileishmanial, anticoagulant, anticonvulsant, antitubercular, antioxidant, antiulcer, CFTR, antimalarials, neuroprotection properties, HIV-1 protease inhibitors, antifertility activities and many more. There are many drugs available in market which contains 1, 4-dihydropyridines ring as basic scaffold. Basic motive of this review is to disclose various therapeutic applications of 1, 4-dihydropyridine derivatives reported by other researchers during their research work in 2001 to 2011.

Angiogenesis is a multistep process for the formation of new blood vessels. Interactions between several cellular factors including growth factors, cytokines and hematopoietic factors lead to activation of various cellular pathways finally resulting in the extracellular matrix (ECM) degradation, endothelial cell proliferation, survival and migration. Normally, angiogenesis is an essential requirement for vascular development in growing embryos as well as in adult tissues where this process depends on the intricate balance between the activities of the pro- and anti-angiogenic factors. Abnormal angiogenesis results in aberrant vasculature leading to various pathological conditions. The most important factor implicated in angiogenic processes is vascular endothelial growth factor (VEGF) and its family of ligands and receptors. Several anti-angiogenic drugs have been developed and many more are currently in different phases of clinical trials, which target various angiogenesis-inducing agents including VEGF, VEGF receptors, angiopoietins and ECM components such as integrins. Anti-angiogenic therapy can be divided into gene-based therapy and protein-based therapy. Gene-based therapies include the use of antisense oligonucleotides, siRNA, aptamers, catalytic oligonucleotides including ribozymes and DNAzymes and transcription decoys. Protein-based therapeutics includes monoclonal antibodies, peptidomimetics, fusion proteins and decoy receptors. The later class of therapeutics has several advantages over gene-based and small molecule drugs, including specificity and complexity in functions, better tolerability, less interference with normal biological processes and lesser adverse effects due to decreased immune response by virtue of being mostly body’s natural proteins. This review provides a comprehensive overview of angiogenesis and on the current protein-based anti-angiogenic therapeutics under research and in the clinic.