The “Warburg effect” provides a novel method for treating cancer cell metabolism. Overexpression of glucose transporter 1 (GLUT1), activation of AMP-activated protein kinase (AMPK), and downregulation of mammalian target of rapamycin (mTOR) have been identified as biomarkers of abnormal cancer cell metabolism. Metformin (MET) is an effective therapy for breast cancer (BC), but its efficacy is largely reliant on the concentration of glucose at the tumor site. We propose a WZB117 (a GLUT1 inhibitor)-OCMC (O-carboxymethyl-chitosan)-MET combo strategy for simultaneous GLUT1 and mTOR targeting for alteration of BC metabolism. WZB117 conjugated polymeric nanoparticles were 225.67 ± 11.5 nm in size, with a PDI of 0.113 ± 0.16, and an encapsulation of 72.78 6.4%. OCMC pH-dependently and selectively releases MET at the tumor site. MET targets the mTOR pathway in cancer cells, and WZB117 targets BCL2 to alter GLUT1 at the cancer site. WZB117-OCMC-MET overcomes the limitations of MET monotherapy by targeting mTOR and BCL2 synergistically. WZB117-OCMC-MET activates AMPK and suppresses mTOR in a Western blot experiment, indicating growth-inhibitory and apoptotic characteristics. AO/EB and the cell cycle enhance cellular internalization as compared to MET alone. WZB117-OCMC-MET affects cancer cells’ metabolism and is a promising BC therapeutic strategy.

An alarming requirement for finding newer antidiabetic glitazones as agonists to PPARγ are on its utmost need from past few years as the side effects associated with the available drug therapy is dreadful. In this context, herein, we have made an attempt to develop some novel glitazones as PPARγ agonists, by rational and computer aided drug design approach by implementing the principles of bioisosterism. The designed glitazones are scored for similarity with the developed 3D pharmacophore model and subjected for docking studies against PPARγ proteins. Synthesized by adopting appropriate synthetic methodology and evaluated for in vitro cytotoxicity and glucose uptake assay. Illustrations about the molecular design of glitazones, synthesis, analysis, glucose uptake activity and SAR via 3D QSAR studies are reported. The computationally designed and synthesized ligands such as 2-(4-((substituted phenylimino)methyl)phenoxy)acetic acid derivatives were analysed by IR, 1H-NMR, 13C-NMR and MS-spectral techniques. The synthesized compounds were evaluated for their in vitro cytotoxicity and glucose uptake assay on 3T3-L1 and L6 cells. Further the activity data was used to develop 3D QSAR model to establish structure activity relationships for glucose uptake activity via CoMSIA studies. The results of pharmacophore, molecular docking study and in vitro evaluation of synthesized compounds were found to be in good correlation. Specifically, CPD03, 07, 08, 18, 19, 21 and 24 are the candidate glitazones exhibited significant glucose uptake activity. 3D-QSAR model revealed the scope for possible further modifications as part of optimisation to find potent anti-diabetic agents.

This review aims at focusing on the use of microneedles (MNs) as an emerging novel drug delivery carrier for an effective treatment in diabetic patients. There are many limitations in various modes of delivery such as oral, subcutaneous, nasal, and other modes which cause pain and have many other side effects. Hence, this drug delivery research has found to have tremendous potential in combining both the diagnostic and therapeutic elements, thus treating diabetes in a better way. Most glucose-sensing techniques and conventional insulin therapies are engaged in the transfer of physical entities through the skin. MN- based drug delivery system can accomplish in an noninvasive or minimally invasive manner which can be an add on advantage towards pain-free administration, easy handling, discrete, continuous as well as providing a controlled release system. Hence, the review addresses on the current advancement of this bioengineered system like MNs, constituting a "smart" system specifically for autonomous diabetes therapy.

Three flavonoid compounds were isolated from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae). On the basis of the chemical and spectral analysis, the compounds were identified as baicalein (Flavone), naringin and neohesperidin (Flavonone). To the best of our knowledge and based on the literature survey all three compounds were first time reported from this medicinal plant.

Background: A newer trend has been seen recently to reuse the conventional drugs with distinct indications for the newer applications to speed up the drug discovery and development based on earlier records and safety data. Most of the non-cancerous agents could afford a little or tolerable side effects in individuals. However, the repositioning of these non-cancerous agents for successful anticancer therapy is an outstanding strategy for future anti-cancer drug development. Since more diverse and selective cancer drug targets are being discovered and developed, the approved drug collections are particularly useful to quickly identify clinically advanced anticancer drugs against those targets. Objective: Antihelminthic drugs such as Mebendazole and Albendazole (Benzimidazole class) have been reported to exhibit cytotoxicity (or anticancer activities) against several types of cancer. Therefore, this study aims to repurpose the benzimidazole scaffold for breast cancer treatment. Methods: In the present study, three hydrazone analogs having a benzimidazole motif in their structural frame were synthesized. Their in-silico binding studies against HER2 receptor (PDB ID: 4LQM) and ADMET studies were carried out using Accelrys drug discovery studio 4.1. Cytotoxicity of the synthesized compounds against HER2 overexpressed MCF-7 cell lines was determined by MTT assay. Results: One of the compounds 2-[2-(2,4-dinitrophenyl)hydrazinylidene]-2,3-dihydro-1H-benzimidazole (U1) has shown good cytotoxicity when compared to the standard Lapatinib, which is a well known HER2 inhibitor. Conclusion: Thus, the designed benzimidazole scaffold might serve as the best leads for treating breast cancer, which is additionally confirmed by performing their docking study via Accelrys discovery studio.