02195nas a2200277 4500008004100000022001400041245011700055210006900172260010600241300001400347490000700361520119800368653001501566653001901581653001201600653001401612653001201626100002201638700001901660700002401679700002201703700001801725700002301743700002801766856012301794 2013 eng d a0960-894X00aCorrelation of hydrogen-bonding propensity and anticancer profile of tetrazole-tethered combretastatin analogues0 aCorrelation of hydrogenbonding propensity and anticancer profile aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a4680-46840 v233 a

A series of 1,5-disubstituted tetrazole-tethered combretastatin analogues with extended hydrogen-bond donors at the ortho-positions of the aryl A and B rings were developed and evaluated for their antitubulin and antiproliferative activity. We wanted to test whether intramolecular hydrogen-bonding used as a conformational locking element in these analogues would improve their activity. The correlation of crystal structures with the antitubulin and antiproliferative profiles of the modified analogues suggested that hydrogen-bond-mediated conformational control of the A ring is deleterious to the bioactivity. In contrast, although there was no clear evidence that intramolecular hydrogen bonding to the B ring enhanced activity, we found that increased substitution on the B ring had a positive effect on antitubulin and antiproliferative activity. Among the various analogues synthesized, compounds 5d and 5e, having hydrogen-bonding donor groups at the ortho and meta-positions on the 4-methoxy phenyl B ring, are strong inhibitors of tubulin polymerization and antiproliferative agents having IC50 value in micromolar concentrations. (C) 2013 Elsevier Ltd. All rights reserved.

10aColchicine10aCombretastatin10aCrystal10aTetrazole10aTubulin1 aJedhe, Ganesh, S.1 aPaul, Debasish1 aGonnade, Rajesh, G.1 aSantra, Manas, K.1 aHamel, Ernest1 aNguyen, Tam, Luong1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/correlation-hydrogen-bonding-propensity-and-anticancer-profile-tetrazole-tethered-001675nas a2200253 4500008004100000022001400041245011200055210006900167260010600236300001400342490000700356520073800363653001501101653001501116653001501131653002001146100002201166700002201188700002401210700002201234700001801256700002801274856011901302 2015 eng d a0960-894X00aNovel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity0 aNovel hybrid nocodazole analogues as tubulin polymerization inhi aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAY a1982-19850 v253 a

We describe the design, synthesis and SAR profiling of a series of novel combretastatin-nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds 1 and 4 showed mu M IC50 values in both assays. (C) 2015 Elsevier Ltd. All rights reserved.

10aAnticancer10aColchicine10aNocodazole10aTubulin binding1 aKale, Sangram, S.1 aJedhe, Ganesh, S.1 aMeshram, Sachin, N.1 aSantra, Manas, K.1 aHamel, Ernest1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/novel-hybrid-nocodazole-analogues-tubulin-polymerization-inhibitors-and-their-002738nas a2200349 4500008004100000022001400041245011300055210006900168260000800237300001400245490000700259520163400266653001201900653001601912653001801928653001801946653001001964653002301974100002201997700001602019700002002035700002902055700002502084700001802109700002002127700001802147700002902165700002202194700002002216700002102236856013102257 2016 eng d a1615-985300aUrinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics0 aUrinary proteome alterations in HER2 enriched breast cancer reve cSEP a2403-24180 v163 a

Globally, breast cancer is the second most common cancer among women. Although biomarker discoveries through various proteomic approaches of tissue and serum samples have been studied in breast cancer, urinary proteome alterations in breast cancer are least studied. Urine being a noninvasive biofluid and a significant source of proteins, it has the potential in early diagnosis of breast cancer. This study used complementary quantitative gel-based and gel-free proteomic approaches to find a panel of urinary protein markers that could discriminate HER2 enriched (HE) subtype breast cancer from the healthy controls. A total of 183 differentially expressed proteins were identified using three complementary approaches, namely 2D-DIGE, iTRAQ, and sequential window acquisition of all theoretical mass spectra. The differentially expressed proteins were subjected to various bioinformatics analyses for deciphering the biological context of these proteins using protein analysis through evolutionary relationships, database for annotation, visualization and integrated discovery, and STRING. Multivariate statistical analysis was undertaken to identify the set of most significant proteins, which could discriminate HE breast cancer from healthy controls. Immunoblotting and MRM-based validation in a separate cohort testified a panel of 21 proteins such as zinc-alpha2-glycoprotein, A2GL, retinol-binding protein 4, annexin A1, SAP3, SRC8, gelsolin, kininogen 1, CO9, clusterin, ceruloplasmin, and alpha 1-antitrypsin could be a panel of candidate markers that could discriminate HE breast cancer from healthy controls.

10a2D-DIGE10aBiomedicine10aBreast cancer10aHER2 enriched10aSWATH10aUrinary biomarkers1 aGajbhiye, Akshada1 aDabhi, Raju1 aTaunk, Khushman1 aVannuruswamy, Garikapati1 aRoyChoudhury, Sourav1 aAdhav, Ragini1 aSeal, Shubhendu1 aMane, Anupama1 aBayatigeri, Santhakumari1 aSantra, Manas, K.1 aChaudhury, Koel1 aRapole, Srikanth uhttps://library.ncl.res.in/content/urinary-proteome-alterations-her2-enriched-breast-cancer-revealed-multipronged-quantitative03488nas a2200241 4500008004100000245011200041210006900153260000800222300000900230490000800239520264200247100002202889700001602911700002002927700003902947700002502986700001803011700002903029700002003058700002203078700002103100856012503121 2017 eng d00aMultipronged quantitative proteomics reveals serum proteome alterations in breast cancer intrinsic subtypes0 aMultipronged quantitative proteomics reveals serum proteome alte cJUN a1-130 v1633 aBeing molecularly heterogeneous, breast cancer tends to be a complicated oncological disease with high incidence rates throughout the world. The primary aim of this study was to identify the set of serum proteins with discriminatory capabilities towards the four major subtypes of breast cancer. We employed multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS and identified 307 differentially regulated proteins. Luminal A subtype consisted of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast cancer subtype 10 differentially regulated subtype specific proteins. These specific proteins were further subjected to bioinformatic tools which revealed the involvement in platelet degranulation, fibrinolysis, lipid metabolism, immune response, complement activation, blood coagulation, glycolysis and cancer signaling pathways in the subtypes of the breast cancer. The significant discrimination efficiency of the models generated through multivariate statistical analysis was decent to distinguish each of the four subtypes from controls. Further, some of the statistically significant differentially regulated proteins were verified and validated by immunoblotting and mass spectrometry based selected reaction monitoring (SRM) approach. Our Multipronged proteomics approaches revealed panel of serum proteins specifically altered for individual subtypes of breast cancer. The mass spectrometry data are available via ProteomeXchange with identifier PXD006441. Biological significance: Worldwide, breast cancer continues to be one of the leading causes of cancer related deaths in women and it encompasses four major molecular subtypes. As breast cancer treatment majorly depends on identification of specific subtype, it is important to diagnosis the disease at subtype level. Our results using multipronged quantitative proteomics identified 307 differentially regulated proteins in which 24 were specific for Luminal A, 38 for Luminal B, 17 for HER2 enriched and 10 proteins were specific for TN subtype. Bioinformatic analysis of these proteins revealed certain biological processes and pathways altered at subtype level and validation experiments of some of these proteins using immunoblotting and SRM assays are consistent with discovery data. This is the first comprehensive proteomic study on serum proteome alterations at subtype level which will not only help to distinguish subtype of breast cancer but also contribute to a better understanding of the molecular characteristic of breast cancer at individual subtype level. (C) 2017 Elsevier B.V. All rights reserved.1 aGajbhiye, Akshada1 aDabhi, Raju1 aTaunk, Khushman1 aJagadeeshaprasad, Mashanipalya, G.1 aRoyChoudhury, Sourav1 aMane, Anupama1 aBayatigeri, Santhakumari1 aChaudhury, Koel1 aSantra, Manas, K.1 aRapole, Srikanth uhttps://library.ncl.res.in/content/multipronged-quantitative-proteomics-reveals-serum-proteome-alterations-breast-cancer01887nas a2200193 4500008004100000022001400041245008700055210006900142260000800211300001400219490000700233520121500240100002801455700001901483700002201502700002201524700002801546856011901574 2020 eng d a1477-052000aSynthesis of artemisinic acid derived glycoconjugates and their anticancer studies0 aSynthesis of artemisinic acid derived glycoconjugates and their  cMAR a2252-22630 v183 a

Glycoconjugates, due to their diverse functions, are widely regarded as biologically important molecules. Artemisinic acid 1 occurs naturally in the plant Artemisia annua and is considered to be the biogenetic precursor of the antimalarial drug, artemisinin 2. We report herein the design and synthesis of diverse artemisinic acid derived glycoconjugates. We have synthesized 12-O-artemisinic acid-glycoconjugates (7a-k) and 12-N-artemisinic acid-glycoconjugates (8a-k) by utilizing Cu(i)-catalyzed azide-alkyne cycloaddition reactions (Click chemistry) with various synthesized sugar azides (6a-k) in good to excellent yields along with two fluorescently labeled compounds, 12-O-artemisinic acid-glycoconjugate 11 and 12-N-artemisinic acid-glycoconjugate 12, to investigate the mode of action of these compounds in biological systems. All the synthesized artemisinic acid glycoconjugates were assayed for their efficacy against the MCF7 cell line. Our anticancer studies indicated that all the synthesized compounds inhibited the growth of MCF7 cells in a dose dependent manner, barring compounds 4 and 7d. However, these compounds exhibit moderate cytotoxicity, as is evident from their IC50 values.

1 aKotammagari, Tharun, K.1 aPaul, Sayantan1 aBarik, Ganesh, K.1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/synthesis-artemisinic-acid-derived-glycoconjugates-and-their-anticancer-studies01599nas a2200277 4500008004100000022001400041245011400055210006900169260000800238300001200246490000700258520068200265653001700947653001800964653002000982653001601002653001901018100002801037700001701065700001901082700001801101700002401119700002201143700002801165856012801193 2023 eng d a1860-539700aAccelerated Rauhut-Currier dimerization enabled the synthesis of (+/-)-incarvilleatone and anticancer studies0 aAccelerated RauhutCurrier dimerization enabled the synthesis of  cFEB a204-2110 v193 a

The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut-Currier (RC) dimeriza-tion. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (+/-)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells nonetheless, they exhibited very limited growth suppression activity.

10adimerization10aincarviditone10aincarvilleatone10aoxa-Michael10aRauhut-Currier1 aKotammagari, Tharun, K.1 aMisra, Sweta1 aPaul, Sayantan1 aKunte, Sunita1 aGonnade, Rajesh, G.1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/accelerated-rauhut-currier-dimerization-enabled-synthesis-incarvilleatone-and-anticancer01407nas a2200241 4500008004100000022001400041245013600055210006900191260000800260300001500268490000700283520054400290653002300834653002900857653002900886653001700915653001800932100001900950700001900969700002200988700002801010856012701038 2025 eng d a2365-654900aCyclopropane containing triterpenoids, cycloartenone, and cycloartenol: isolation, chemical transformations, and anticancer studies0 aCyclopropane containing triterpenoids cycloartenone and cycloart cMAR ae2024036980 v103 a

Cycloartenone and cycloartenol, two plant-derived triterpenoids possessing cyclopropane ring were isolated from the latex of Artocarpus heterophyllus (jackfruit). Cycloartenol was chemically modified to synthesize dihydrocycloartenol via acetylation and deacetylation methodology followed by hydrogenation. Hydroxyl group present in the cycloartenol was also employed for the nitro benzoate formation. All the isolated and synthesized compounds were assayed against MCF7 breast cancer cell line for their anticancer properties.

10aAnticancer studies10aArtocarpus heterophyllus10aChemical transformations10aCycloartenol10aCycloartenone1 aPaul, Sayantan1 aMandal, Kartik1 aSantra, Manas, K.1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/cyclopropane-containing-triterpenoids-cycloartenone-and-cycloartenol-isolation-chemical