02301nas a2200253 4500008004100000020004100041245008500082210006900167260006500236520141300301653001501714653002201729653001501751653001901766653002501785100001601810700001801826700001801844700002101862700002001883700001201903700001201915856012001927 2022 eng d a978-1-5106-4740-4; 978-1-5106-4739-800aSkin mimicking solid optical tissue phantom fulfillment and its characterization0 aSkin mimicking solid optical tissue phantom fulfillment and its  a1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USAbSPIE3 a

Skin mimicking optical tissue phantoms are widely used in diagnostics systems for characterization, optimization, routine calibration and validation. In general, solid phantoms are more preferred in comparison to liquid phantoms. Therefore, our aim is to prepare and characterize the solid tissue phantoms having skin equivalent optical properties. In this work, we have used epoxy resin and hardener as a base material and titanium oxide (TiO2) nanoparticles and ink as a scatterer and absorber media, respectively. The total transmission (Tt), collimated transmission (Tc), and diffuse reflectance (Rd) spectra of the developed phantoms were measured with an integrating sphere installed in UV-VIS spectrometer within the wavelength range 400-700 nm. To characterize the optical properties such as absorption (mu(a)), reduced scattering (mu(s)'), and anisotropy factor (g) of the developed tissue phantoms, the numerical model based on Inverse Adding Doubling (IAD) has been used. With various concentrations of absorber and scatterer, a calibration curve was prepared. The calculated experimental optical properties from IAD matched with the predicted intrinsic optical properties of the skin. Thus, the preliminary results suggest that the recipe used in this study may be used as an alternative approach to developing skin mimicking solid optical phantom for diagnostics system applications.

10aAbsorption10aanisotropy factor10ascattering10askin mimicking10asolid tissue phantom1 aKumar, Ajay1 aHinge, Sarika1 aDixit, Hemant1 aKanawade, Rajesh1 aKulkarni, Gauri1 aChoi, B1 aZeng, H uhttps://library.ncl.res.in/content/skin-mimicking-solid-optical-tissue-phantom-fulfillment-and-its-characterization02594nas a2200349 4500008004100000022001400041245019200055210006900247260000900316300001100325490000800336520142000344653001501764653001001779653002001789653002001809653002101829653001701850100001801867700002001885700001801905700002101923700002401944700002301968700001901991700002202010700001602032700002402048700002402072700002102096856012702117 2023 eng d a0223-523400aSynthesis, biological evaluation and docking studies of silicon incorporated diarylpyrroles as MmpL3 inhibitors: an effective strategy towards development of potent anti-tubercular agents0 aSynthesis biological evaluation and docking studies of silicon i cNOV  a1156330 v2593 a

Growing global demand for new molecules to treat tuberculosis has created an urgent need to develop novel strategies to combat the menace. BM212 related compounds were found to be potent anti-TB agents and they inhibit mycolic acid transporter, MmpL3, a known potent drug target from Mycobacterium tuberculosis. In order to enhance their inhibitory potency, several silicon analogues of diarylpyrroles related to BM212 were designed, synthesized, and evaluated for anti-tubercular activities. In Alamar blue assay, most of the silicon-incorporated compounds were found to be more potent than the parent compound (BM212), against Mycobacterium tuberculosis (MIC = 1.7 & mu;M, H37Rv). Docking results from the crystal structure of MmpL3 and silicon analogues as pharmacophore model also strongly correlate with the biological assays and suggest that the incorporation of silicon in the inhibitor scaffold could enhance their potency by stabilizing the hydrophobic residues at the binding pocket. The best docking hit, compound 12 showed an MIC of 0.1 & mu;M against H37Rv with an acceptable in vitro ADME profile and excellent selectivity index. Overall, the present study indicates that, the designed silicon analogues, especially compound 12 could be a good inhibitor for an intrinsically flexible drug-binding pocket of MmpL3 and has potential for further development as anti-tubercular agents.

10aantibiotic10aBM21210adocking studies10aMmpL3 inhibitor10aSilicon analogue10atuberculosis1 aVasudevan, N.1 aMotiwala, Zenia1 aRamesh, Remya1 aWagh, Sachin, B.1 aShingare, Rahul, D.1 aKatte, Revansiddha1 aAnand, Amitesh1 aChoudhary, Sushil1 aKumar, Ajay1 aGokhale, Rajesh, S.1 aKulkarni, Kiran, A.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-docking-studies-silicon-incorporated-diarylpyrroles02244nas a2200253 4500008004100000245011300041210006900154260000800223300001400231490000700245520136600252100002501618700002801643700002401671700001801695700001901713700002901732700002001761700001601781700001701797700002401814700002101838856013101859 2025 eng d00aSilicon incorporated tacrine: design, synthesis, and evaluation of biological and pharmacokinetic parameters0 aSilicon incorporated tacrine design synthesis and evaluation of  cJUN a2603-26140 v163 a

Tacrine, an orally bioavailable cholinesterase inhibitor, was previously used to treat Alzheimer's disease but was withdrawn due to hepatotoxicity. The unique structural features of tacrine have once again captured the interest of medicinal chemists. However, the blood-brain barrier (BBB) permeability hampered the development of the majority of its new analogs. Herein, we employed a silicon switch approach for improving the BBB permeability of CNS drugs with tacrine as a tool compound. The replacement of C2 methylene of tacrine with dimethyl silicon yielded `sila-tacrine' that inhibits acetylcholinesterase as well as butyrylcholinesterase with IC50 values of 3.18 and 6.09 mu M, respectively. Sila-tacrine competitively inhibits acetylcholinesterase while it is a non-competitive inhibitor of butyrylcholinesterase. The molecular docking results corroborated with the in vitro cholinesterase inhibition activity of tacrine vs. sila-tacrine. Sila-tacrine demonstrated metabolic stability in HLM and MLM and exhibited superior plasma exposure in an oral pharmacokinetic study in Swiss albino mice. However, tissue distribution studies revealed lower-than-expected brain levels due to efflux pump-mediated transport. This study offers a proof-of-concept for the silicon switch approach in improving the BBB permeability of CNS-active compounds.

1 aKulkarni, Akshay, S.1 aRamana, Sreenivasa, Rao1 aNuthakki, Vijay, K.1 aBhatt, Shipra1 aJamwal, Ashiya1 aNandawadekar, Laxman, D.1 aJotshi, Anshika1 aKumar, Ajay1 aNandi, Utpal1 aBharate, Sandip, B.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/silicon-incorporated-tacrine-design-synthesis-and-evaluation-biological-and-pharmacokinetic