Mini Reviews in Medicinal Chemistry - Volume 17, Issue 14, 2017

Background: P-glycoprotein (Pgp) is well known for its clinical importance in the pharmacokinetics of drugs and its role in multidrug resistance. The promiscuity of Pgp that arises from its ability to extrude a wide range of lipophilic and structurally unrelated compounds from cells, render the classification and understanding of its interacting compounds a great challenge. Method: In this study, a data set of Pgp-interacting compounds including 1463 inhibitors, 1085 noninhibitors, 308 substrates and 126 non-substrates was retrieved and subjected to a combination of analyses, including exploration of chemical space, statistical analysis of descriptor values and molecular fragment analysis, to obtain insight into distinct physicochemical properties and important chemical substructures which may govern the biological activity of investigated compounds toward Pgp. Statistical analysis of descriptor values and molecular fragment analysis indicated that particular size, shape, functional groups and molecular fragments may govern the classification of Pgp-interacting compounds by influencing their physicochemical properties and their interaction with Pgp. Overall, the interacting compounds (i.e., substrates and inhibitors) are larger in size, more flexible, more lipophilic, and less charged than non-interacting compounds (i.e., non-substrates and non-inhibitors). Conclusion: The fragment analysis suggested that methyl and amino groups may be involved in Pgp inhibition and/or transport. The 2-methoxyphenol fragment was noted to be a potential substructure for designing Pgp inhibitors, whereas the 2-sulfanylidene-1-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2- yl]-1,2-dihydropyridine-3-carbonitrile substructure was implied for avoiding transport by Pgp. Hence, this study could provide a comprehensive understanding of this drug transporter, which could benefit an early ADMET screening as well as drug design and development.

Background: Benign prostatic hyperplasia (BPH), the most common condition in aging men is the non cancerous proliferation of epithelial and stromal cells of the prostate gland and is associated with lower urinary tract symptoms (LUTS) such as frequency hesitancy urgency etc. Sources of symptoms in patient with BPH appear to be both static and dynamic component. Better understanding of the prostate physiology, function and pathogenesis has lead to the development of promising agents, useful in the management of lower urinary tract symptoms in men. Objective: Treatment of clinical BPH aims to improve symptoms, prevent urinary tract infections, avoid renal insult, relief obstruction and improve bladder emptying. Many herbal formulations, or plant derived non-nutritive compounds with protective or disease preventive properties are getting popularized worldwide for the management of BPH, especially due to long term side effects of pharmacological treatment and risk of mortality associated with surgical procedures. Phytotherapeutic preparations are plant extracts with different components obtained by different extraction procedures. Numerous mechanisms of action have been postulated for mono and combination plant extracts. Conclusion: This article give a brief account of rationale and efficacy of various existing phytotherapeutic agents in the management of benign prostatic hyperplasia, including the herbs which hold the potential promise are also mentioned, although much research is still required.

Background: Multiple strategies have been recommended for prevention and control of antibacterial resistance. Solutions will need to be found soon if we are not to run the serious risk of losing the ability to treat bacterial infections, especially the ones arising from multi-resistant strains. Deep knowledge of the resistance mechanisms followed by novel therapeutic drugs and vaccines are needed. A consolidated, multidisciplinary and regulated strategy is required by this challenge. Objective: This review will be focused on new strategies to control infections. Among strategies to tackle antibiotic resistance that have been under investigation, are the use of antimicrobial peptides, phage therapy and phage enzymes, therapeutic antibodies, quorum sensing inhibitors and, finally, the antibacterial nanomedicines. Although all of the approaches seem to be effective, and at least one of them has been in use for relatively a long time (phage therapy), antibacterial nanomedicines show the most diverse range of different approaches regarding potential translation to clinics. Results & Conclusion: Several advances have been made but a great effort is still mandatory in order to reach feasible, effective and marketable novel antimicrobial products.

Background: Flavonoids and chromones are two important classes of natural products that have various biological properties. During the past 10 years, there has been a significant increase in studies on the one-pot synthesis of flavonoids and chromones as medicinal scaffolds in drug discovery. Objective: This review describes the scope, mechanistic properties and regio- and chemo-selectivity features of several recently developed one-pot procedures for the synthesis of substituted chromones and flavonoids that have recently been published. Special importance is placed on the most promising and exciting medicinal applications of flavonoids and chromones. In this review, we discuss the progress on the synthesis of flavonoid and chromone derivatives in the presence of metal catalysts, organocatalysts, solid surfaces, microwave irradiation, acid and base catalysis, etc. For example, flavones can be prepared via the catalytic coordination of palladium complexes in a short time and at a low temperature with a high yield. Result: Additionally, the one-pot synthesis of 2-substituted chromones via metal triflate (Yb(OTf)3) has provided the best result for this type of reaction with a high yield and a high regio and chemoselectivity. Generally, this review proposes the first specific overview of this developing and rapidly expanding field of flavonoid synthesis. We also discuss the mechanisms and advantages and disadvantages of methods for the synthesis of flavonoids and chromones.

Objective: Synthetic anionophores are created to mediate the transmembrane transport of anions across phospholipid bilayer membranes. By replacing the defective natural anion channels, they are thought to have high potentials as chemotherapeutic agents for the treatment of channelopathies. Method: In addition, there is a hope that synthetic anionophores may serve as therapeutic agents for cancers and bacterial infections. Because of the amphiphilicity of phospholipid bilayer membranes, lipophilicity has been well studied as one of the most important structural factors that affect the activity of synthetic anionophores. This paper reviews the application of lipophilic balance modification in the creation of effective synthetic anionophores during the past few years. Conclusion: The strategies that have been widely used to change the lipophilicity are introduced. In addition, the important role of optimal lipophilicity in terms of logP in the rational design of synthetic anionophores is also discussed.

Background & Objective: Semiconductor quantum dots proved themselves as efficient fluorescent probes in cancer detection and treatment. Their size, high stability, non-photobleaching and water solubility made them a unique fluorophore in place of conventional organic dyes. Method: Newly emerged theranostic drug delivery system using quantum dots helped us in better understanding of the drug delivery mechanism inside the cells. Surface modified Quantum dots and their applications became wide in bioimaging, immunohistochemistry, tracking intracellular drug and intracellular molecules target. Conclusion: We have highlighted various applications of quantum dots in cancer treatment, drug delivery, flow cytometry, and theranostics.