DITHIOCARBAMATE SUBSTITUTED PHENOTHIAZINE DERIVATIVES: IN SILICO EXPERIMENTS, SYNTHESIS, AND BIOLOGICAL EVALUATION

Objective: The present study was designed to study the anticancer activity of a series of novel analogs of phenothiazine with dithiocarbamate as a side chain. Methods: A novel series of derivatives containing dithiocarbamate as a side chain at the tenth position of phenothiazine nucleus were synthesized, characterized by spectral analysis, and evaluated for their antimitotic and antioxidant activity using germinated Bengal gram seeds and 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, respectively. A quantitative estimate of drug-likeness was also performed, which calculated the molecular properties and screened the molecules based on drug-likeness rules. Further, molecular docking study was performed for finding the binding affinity with tubulin protein to rationalize their anticancer activity. Results: The results revealed that the antioxidant activity of compounds 3e, 3g, 3i, 3j and standard Ascorbic acid were 10 mmol, 14 mmol, 16 mmol, 16 mmol and 35 mmol, respectively. Further compounds 3e, 3g, 3h and 3i have shown promising antimitotic activity. Compound 3i (-9 K. Cal/mol) showed the highest binding energies towards tubulin protein when compared to standard drug colchicine (-8.6 K. Cal/mol). Among all, compound 3i showed promising antimitotic and antioxidant activity, which correlated with insilico docking studies. Conclusion: Dithiocarbamate substituted phenothiazine derivatives proved to be encouraging leads as tubulin inhibitors

Static and pseudo-static stability analysis of right earthen embankment of nagarjuna sagar dam by geostudio

To ensure the safety of the dam, stability assessment of the dam is necessary. The objective is to perform slope stability analysis for upstream, downstream and seepage analysis during steady state, transient seepage conditions and to know about the displacement occurred at history nodes by the application of pseudo-static ground motion. The present work deals with the behavior of the Right earthen embankment of Nagarjuna Sagar which is in earthquake prone area of Zone-II (as per IS 1893-2002). Stability parameters slope, seepage and earthquake analyzed by SLOPE/W, SEEP/W, QUAKE/W tools in GeoStudio 2022 (finite element modeling based software). The model with full reservoir level is first analyzed by SEEP/W to find piezometric line which is basis to perform SLOPE/W for finding slope stability. Later an earthquake motion of 0.1 peak ground acceleration is subjected to it by using QUAKE/W. It is concluded from results, that obtained factor of safety lie within safety limits and seepage loss observed during the design life of 100 years is 562290 m3, 3431117 m3 for steady state and rapid drawdown

Engineering Highly Stable, Fluorescent and Non-toxic Cu Nanoclusters via Reaction Parameter Optimization

Metal Nanoclusters (NCs) composed of the least number of atoms (few to tens) became very attractive for their emerging properties owing to their ultrasmall size. Preparing copper nanoclusters (Cu NCs) in an aqueous medium with high emission properties, strong colloidal stability, and low toxicity has been a long-standing challenge. Although they are earth-abundant and inexpensive, they are comparatively less explored due to their limitations such as ease of surface oxidation, poor colloidal stability, and high toxicity. To overcome these constraints, we established a facile synthetic route by optimizing the reaction parameters, especially altering the effective concentration of the reducing agent to influence their optical characteristics. The improvement of photoluminescence intensity and superior colloidal stability was modeled from a theoretical standpoint. Moreover, the as-synthesized Cu NCs showed a significant reduction of toxicity in both in vitro and in vivo models. The possibilities of using such Cu NCs as a diagnostic probe towards C. elegans were explored. Also, the extension of our approach towards improving the photoluminescence intensity of the Cu NCs on other ligand systems was demonstrated

Potential impact of various surface ligands on the cellular uptake and biodistribution characteristics of red, green, and blue emitting Cu nanoclusters

Surface functionalization has a prominent influence on tuning/manipulating the physicochemical properties of nanometer scaled materials. Ultrasmall sized nanoclusters with very few atoms have received enormous attention due to their bright fluorescence, biocompatibility, lower toxicity, good colloidal stability and strong photostability. These properties make them suitable for diagnostic applications. In this work, we intend to study the effect of surface functional ligands on their biodistribution both in vitro and in vivo organelle systems for bioimaging applications.Published versionS. C. acknowledges the financial support from University Grant Commission-Department of Atomic Energy (UGC-DAE) Consortium for Scientific Research, (UGC-DAE-CRS/2021-22/02/513) and Science and Engineering Research Board (SERB) under State University Research Excellence (SUR/2022/001424)