2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: rational identification of a new anticancer lead

Hsp90 is a molecular chaperone that heals diverse array of biomolecules ranging from multiple oncogenic proteins to the ones responsible for development of resistance to chemotherapeutic agents. Moreover they are over-expressed in cancer cells as a complex with co-chaperones and under-expressed in normal cells as a single free entity. Hence inhibitors of Hsp90 will be more effective and selective in destroying cancer cells with minimum chances of acquiring resistance to them. In continuation of our goal to rationally develop effective small molecule azomethines against Hsp90, we designed few more compounds belonging to the class of 2,4-dihydroxy benzaldehyde derived imines (1-13) with our validated docking protocol. The molecules exhibiting good docking score were synthesized and their structures were confirmed by IR, (1)H NMR and mass spectral analysis. Subsequently, they were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The antiproliferative effect of the molecules were examined on PC3 prostate cancer cell lines by adopting 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. Finally, schiff base 13 emerged as the lead molecule for future design and development of Hsp90 inhibitors as anticancer agents.Fil: Dutta Gupta, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; IndiaFil: Revathi, B.. Osmania University; IndiaFil: Mazaira, Gisela Ileana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Subrahmanyam, C. V. S.. Osmania University; IndiaFil: Gowrishankar, N. L.. Swami Vivekananda Institute of Pharmaceutical Sciences; IndiaFil: Raghavendra, N. M.. Osmania University; Indi

Arsenic contaminated water remediation: A state-of-the-art review in synchrony with sustainable development goals

Arsenic (As) is a highly abundant metalloid with detrimental effects on ecosystems and human health. Several research works have focused on the development and application of suitable materials capable of removing arsenic effectively from water. In this regard, nano-materials have been given considerable importance due to their unique properties. In addition to nano-materials, single, multi and doped metal oxides have also received substantial attention because of their high surface-to-volume ratio, increased magnetic properties, catalytic properties, etc. These metal oxides have been developed using several methods like solid state reaction, vapour deposition, chemical precipitation, etc. among which chemical precipitation is quite user friendly. Single and mixed metal oxides have been applied widely in arsenic removal since they usually have high arsenic adsorption capacity. Several biomaterials including biochar showed promising results in arsenic removal from water. Desorption studies showed that NaOH, KOH were effective in regenerating the adsorbents from the nanomaterials. Graphene based materials usually show very high surface area due to their open structure, thus, they are effective materials in arsenic removal from water. Water treatment using nanomaterials can be one of the sustainable solutions and in synchrony with Goal 6 in UN Sustainable Development Goals (SDGs), which aims to ensure availability and sustainable water management and sanitation for the global population. Nevertheless, there is a significant research gap between the application of these nano-materials in laboratory settings and their real-world field conditions. Additionally, only a limited number of studies have investigated the potential effects of these nanomaterials on the environment and living organisms. However, by carefully selecting appropriate materials and conducting thorough environmental risk assessments, we can overcome these challenges and move towards successful implementation of long term arsenic remediation

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model

Senolytic potential of Hsp90 inhibitors

: Hsp90 chaperone is an encouraging target for the development of novel anticancer agents. The failure of Hsp90 inhibitors to get regulatory approval for the treatment of cancer is hindered due to toxicity, cost involved in their development and formulation issues. The inhibitors against this chaperone is also being evaluated in pre-clinical models for the treatment of diseases other than cancer (Alzheimer, malaria, AIDS, etc.). Recently, Hsp90 inhibitors have shown promising senolytic effect, that is helpful in increasing the health and life span of mice. The senolytic property of Hsp90 inhibitors will make them less toxic for use in humans. The review focuses on Hsp90 inhibitors discovered till date as senolytic agents along with their future prospects. Further, the various models used for the evaluation of senolytic effect are also discussed. </jats:sec