Mini Reviews in Medicinal Chemistry - Volume 18, Issue 11, 2018

Sinomenine is one of the most widely known alkaloids owing to different therapeutic properties including anti-inflammatory and immunosuppressive activities, as well as the potency in neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Sinomenine has been studied as a potential anti-inflammatory agent through appropriate structural modifications. Recently, a number of such approaches have been attempted in various laboratories with great success. Several series of derivatives have been synthesized with changes at rings A, B, C and D. Herein, we present an up to date review of modifications and bioactivities of important modified derivatives. These studies offer interesting knowledge on the bioactivity and structural specificity of sinomenine, providing better understanding of the structure-activity relationships (SAR) between designing and development of sinomenine derivative with better therapeutic and lower side effects.

Pyrazole nucleus is a unique structural scaffold which acts as an interesting template for combinatorial as well as medicinal chemistry. This review presents a detailed overview on the synthesis, QSAR and pharmacological applications of pyrazole. In addition, it covers most recent reports on structural modifications on pyrazole illustrating vital structural activity relationship.

At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have exhibited wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery. Here, we review some deadly defects of clinical medicines to the therapy of diseases and important advances on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral, antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer Disease), indicating that rhodanine heterocycle could be used as a significant pharmacophore to develop novel pharmacological active molecules. It is believed that the review is of importance for new ideas in the development of and rational designs of rhodanine-based drugs.

The pharmacological targeting of microcirculatory dysregulations is a therapeutic strategy for the treatment of numerous pathological conditions, such as cancer, thrombosis and inflammation. A promising candidate for this purpose is indole-3-carbinol (I3C), a phytochemical compound of cruciferous vegetables, and its main derivate 3,3,'-diindolylmethane (DIM). As summarized in this review, I3C and DIM affect multiple molecular and cellular processes within the microcirculation due to their pleiotropic action profile. These include angiogenesis, leukocyte-endothelial cell interaction, cytokine and reactive oxygen species (ROS) production, thrombus formation and microvascular leakage. Hence, I3C may serve as a lead compound for the future chemical synthesis of novel drugs that exert comparable beneficial effects while exhibiting an improved bioavailability.

Theranostic agents or theranostic imaging as its name suggests is a combination of two terms-‘diagnosis’ & ‘therapy’. Efforts are being made to combine both the terms into clinical formulations. This theranostic imaging is found to be very much significant to complex diseases like cancer and proliferative tumors especially because accurate photocopy for every tumor can be obtained by genomic and proteomic profiling and using such informations in theranostic agents can be constructed or modeled in such a way that it is specific in its action and selective towards the cancer cells only, without causing any adverse effects on the normal tissue cells. By means of nanoplatforms, we can conveniently deliver cancer cell specific targeting ligand or peptide inside the human body. Primary delivery approach comprises of nanoparticles, liposomes, dendrimers, prodrugs, polymersomes, carbon nanotubes and polymeric micelles. Theranostic agents, i.e., therapeutic and diagnostic agents can be physically bound or else they can be bound with polymers which are exclusively designed and this together forms nanocarriers. Hence, the review highlights the advances of nanotechnology that has given us a platform for cancer detection and treatment.

Mesoporous silica nanoparticles (MSNs) are exceptionally promising drug carriers for controlled drug delivery systems because their morphology, pore structure, pore volume and pore size can be well tailored to obtain certain drug release profiles. Moreover, they possess the ability to specifically transport and deliver anti-cancer drugs when targeting molecules are properly grafted onto their surface. MSNs based drug delivery systems have the potential to revolutionize cancer therapy. This review provides a comprehensive overview of the fabrication, modification of MSNs and their applications in tumour-targeted delivery. In addition, the characterization and analysis of MSNs with computer aided strategies were described. The existing issues and future prospective concerning the applications of MSNs as drug carriers for controlled drug delivery systems were discussed.