Mini Reviews in Medicinal Chemistry - Volume 17, Issue 15, 2017

Background: Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The autoreactive B cells and T helper cells together are known to develop adverse immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy. Method: The prospect of B cell depletion by CD20 targeted monoclonal antibody Rituximab has been demonstrated in lupus patients. The CD52 specific monoclonal antibody Alemtuzumab is another proposition for lupus therapy. The drug Belimumab inhibits B cell activation by altering BAFF/APRIL signal cascade. Recent discovery of the CD22 targeted Epratuzumab also shows therapeutic prospect. The researches on new generation drugs for autoimmune lupus include search for inhibitors of CD40- CD40Ligand interactions, CD86 activation, selective modulation of complement cascades. The choice of inhibitors of transcription factor NF-ΚBp65 and selective modulators for estrogen receptor alpha are proposed areas of lupus drug discovery research. Results & Conclusion: Keeping a close eye on the mechanisms of disease onset, a comprehensive view is provided on recent therapy of systemic lupus erythematosus.

Background: This is a short review on the most recent studies on curcumin and its analogs, including the studies from the laboratories of authors. The diverse medicinal properties of curcumin itself reported in the recent years are reviewed. Although curcumin has shown great potential in treating various diseases, it has not been approved as a clinical drug candidate because of its poor pharmacokinetics. Method: The recent methods developed to solve this problem are briefly described. Conclusion: The biological and other properties of synthetic curcumin analogs (diarylheptanoids and diarylpentanoid monocarbonyl derivatives) reported in the recent literature are also presented.

Background: Cancer is one of the main causes of death worldwide. Breast cancer is the most prevalent type of cancer in women and the leading cause of cancer deaths due to its high metastasis to the lymph nodes, lungs bones and brain. Interactions with the stromal microenvironment surrounding tumor cells facilitate tumor cell migration and invasion of tissues and dissemination to other organs, to form metastasis. The development of antitumor metal-based drugs was originated with the discovery of cisplatin, however, its severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as promising antitumor drugs. Conclusion: In this review, we focused on the effects of Ru complexes on breast cancer cells and their impact on different steps of the metastatic process.

Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund’s complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. Results & Conclusion: In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed.

Background: Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. Conclusion: This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery. Highlights: • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors.

Background: Thiazolopyrimidine derivatives containing bridgehead nitrogen atom are nowa- days attracting the attention of many medicinal chemists throughout the world to explore this framework for its potential. This biologically important scaffold is formed by the fusion of two aromatic rings, thiazole and pyrimidine, in such a way that one carbon atom at the ring junction is replaced by a nitrogen atom and is, therefore, being common for both the heterocyclic rings. One of the most common example of this type of fusion is thiazolo[3,2-a]pyrimidine which is being used perpetually with tremendous success in various fields of therapeutic applications. Method: Despite the outstanding researches on thiazolo[3,2-a]pyrimidines in the literature, hardly there is a comprehensive review on the chemistry and medicinal values of present scaffold. This review is, therefore, to endow with highlights on assorted progress made over the recent past on the basis of the development of new synthetic strategies, structure of various synthesized molecules and their promising medicinal attributes. Conclusion: In addition, we have undertaken various scientific reports in depth, to explain spectral characterization (UV, IR, Mass, NMR and X-ray crystallography) and stereochemistry, particularly of thiazolo[3,2-a]pyrimidines.