01841nas a2200265 4500008004100000022001400041245009000055210006900145260007900214300000800293490000700301520090900308653002601217653002501243653002401268653002201292653002501314653002201339653001601361100002001377700002401397700001901421700001601440856011901456 2014 eng d a1093-326300aMolecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets0 aMolecular recognition pattern of cytotoxic alkaloid vinblastine  a360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USAbELSEVIER SCIENCE INCcNOV a1-90 v543 a

Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM-MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation-pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors. (C) 2014 Elsevier Inc. All rights reserved.

10aDrug-DNA interactions10aDrug-protein binding10aHuman serum albumin10aMolecular docking10aMultitarget affinity10aQM-MM calculation10aVinblastine1 aPandya, Prateek1 aAgarwal, Lokesh, Kr1 aGupta, Neelima1 aPal, Sourav uhttps://library.ncl.res.in/content/molecular-recognition-pattern-cytotoxic-alkaloid-vinblastine-multiple-targets-002416nas a2200229 4500008004100000022001400041245011700055210006900172260000800241300001100249490000800260520165100268653001701919653002401936653001301960653001901973100001701992700001402009700001502023700001702038856013102055 2019 eng d a0039-128X00aSteroidal thiazolidinone derivatives: design, synthesis and their molecular interaction with human serum albumin0 aSteroidal thiazolidinone derivatives design synthesis and their  cAUG a99-1130 v1483 a

A series of steroidal thiazolidinone derivatives have been synthesized through one-pot multicomponent reaction involving steroidal ketone, thiosemicarbazide/methyl-thiosemicarbazide and DMAD in presence of AlCl3 as a Lewis acid catalyst. Among all the synthesized steroidal thiazolidinone derivatives, compound 7-9 (ST 7-9) were investigated for their in vitro molecular interaction with human serum albumin. Intrinsic fluorescence spectroscopy, constant wavelength synchronous fluorescence spectroscopy, circular dichroism and UV-visible absorption techniques have been exploited to characterize the binding phenomena in phosphate buffer solution at pH 7.4. The experimental results indicated that ST 7-9 bind to HSA and the intrinsic fluorescence of HSA was quenched through static quenching mechanism. The binding parameters were calculated and the binding constants obtained were 1.44 x 10(5) M-1 for ST 7, 0.84 x 10(5) M-1 for ST 8 and 1.06 x 10(5) M-1 for ST 9. Circular dichroism analysis confirms that the presence of ST 7-9, altered the secondary structure of HSA due to partial unfolding of the polypeptide chain. Furthermore, hemolytic activity assay demonstrated that the synthesized steroidal thiazolidinone derivatives have good compatibility towards human red blood cells. Finally, molecular docking studies revealed that the steroidal thiazolidinones can bind in the hydrophobic cavity of HSA, by hydrophobic and hydrogen bonding interaction. These results provided valuable information about the binding mechanism of ST 7-9 with HSA and play a pivotal role in the development of steroidal heterocycle inspired compounds.

10aheterocycles10aHuman serum albumin10asteroids10aThiazolidinone1 aAnsari, Anam1 aAli, Abad1 aAsif, Mohd1 aShamsuzzaman uhttps://library.ncl.res.in/content/steroidal-thiazolidinone-derivatives-design-synthesis-and-their-molecular-interaction-human02333nas a2200289 4500008004100000022001400041245007800055210006900133260000800202300001100210490000800221520142300229653001401652653002401666653002401690653002201714653003301736653002201769100001801791700001601809700002401825700002201849700002001871700002501891700002001916856010701936 2024 eng d a0141-813000aMulti-dimensional impact of captopril modification on human serum albumin0 aMultidimensional impact of captopril modification on human serum cAUG a1332890 v2743 a

Captopril is a thiol drug, widely used for the management of hypertension and cardiovascular diseases. Reactive thiols are found to covalently modify the cysteines of plasma proteins and affect their structure and function. Human serum albumin (HSA) is prone to undergo modification by various low molecular weight compounds, including drugs. Cysteine34 (Cys34) in HSA has a free thiol group with antioxidant properties, considered to be the most redox-sensitive amino acid in plasma. Through mass-spectrometric analysis, we demonstrate for the first time that captopril forms a disulfide adduct at Cys34 residue and increases the protease susceptibility of HSA to trypsin. As evidenced by our biophysical and electron microscopy studies, HSA undergoes structural alteration, aggregation and morphological changes when treated with different captopril concentrations. Molecular dynamics studies further revealed the regions of secondary structural changes in HSA due to disulfide adduct formation by captopril at Cys34. It also elucidated the residues involved in the noncovalent interactions with captopril. It is envisaged that structural change in HSA may influence the efficacy of drug delivery as well as its own biological function. These findings may thus provide significant insights into the field of pharmacology intriguing further investigation into the effects of long-term captopril treatment.

10aCaptopril10aElectron microscopy10aHuman serum albumin10aMass spectrometry10aMolecular dynamic simulation10aSpectrophotometry1 aGhosh, Amrita1 aJani, Vinod1 aSonavane, Uddhavesh1 aNaphade, Anvi, N.1 aJoshi, Rajendra1 aKulkarni, Mahesh, J.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/multi-dimensional-impact-captopril-modification-human-serum-albumin