A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.

Background The phosphatidylinositol 3-kinase (PI3K) signallingpathwayplays crucial roles in cell growth, proliferation and survival, and found frequently dysregulatedpathwayinlungcancer.Consequently,1,3,5-triazinebasedinhibitorsof key kinases in the pathway, including PI3K, AKT and mTOR, have been extensively pursuedinoncologyinrecentyears.ThePI3K-Akt-mTORpathwayiscommonly deregulated in human malignancy including NSCLC. Therefore, the present study was aimedtodevelop novel1,3,5-triazinederivativesasdualPI3K/mTOR forlung carcinoma. Methods:The1,3,5-triazinecompoundsweresynthesizedviamulti-component reaction. Thecompounds weretestedfordetermination ofanticanceractivityagainst three human NSCLC cell lines A549, H157 and H52. The compounds were also tested for effect on cell growth inhibition and apoptosis through cell cycle arrest assay. The compounds were tested for inhibitory activity against PI3Ka and mTOR via kinase inhibition assay. The docking analysis was also carried out with PI3K and mTOR domain to elucidate vital structural residues necessary for bioactivity. Results The compounds were developed in excellent yield. The cytotoxicity studies suggests that, synthesized derivatives exhibit considerable inhibition with average IC50 forcompound7hwerefoundtobe1.21,2.03and2.86mmol/lagainstA549,H157and H52 cells, respectively. The compound 7h causes a significant increase in the number of cells in G0-G1 phase, withacorrespondingdecrease in the number ofcells in S and G2- Mphase.Itinducestumorcellapoptosisinadose-dependentmanner.Thecompound 7h,showedIC50of3.2360.23mMand1.2160.15againstPI3KsandmTOR, respectively. Whereas, the docking results showed that compound 7h, 7l, 7m, 7e were found to be the most efficient analogues to inhibit PI3Ks and mTOR by binding the ATP pocket via creating interactions with ASP2195, ASP2357, LYS802 and ASP810. Conclusions:Inconclusion,1,3,5-triazine-thioureahasshownpromisingantitumor activityviaattenuationofPI3K/mTORagainstNSCLCandrepresentspotential therapeutic application for further development. Legal entity responsible for the study SHIATS Funding SHIATS Disclosure All authors have declared no conflicts ofinterest.

We have recently moved into an era not just of multiple resistant bacteria but of totally resistant pathogens, which now include vancomycin-resistant enterococci, carbapenem-resistant Acinetobacter baumannii, vancomycin-resistant MRSA and, very recently, NDM-1. Thus, increased incidence of bacterial resistance to currently available antibiotics necessitates the discovery and introduction of new and effective drugs. In our earlier studies, we have discovered a potent antibacterial lead molecule from 1,3,5-triazine (first generation) and its subsequent optimization till its tenth generation results much more advanced analogue with enhanced activity and less toxicity [1].

A series of hybrid thiazolidin-4-one-1,3,5-triazines was evaluated for NF-κB, biofilm and CFTR activity.

A novel series of 1,3,5-triazine-thiazolidine-2,4-diones was synthesized and characterized by a number of analytical and spectroscopic techniques.