<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Aarthy, Thiagarayaselvam</style></author><author><style face="normal" font="default" size="100%">Mulani, Fayaj A.</style></author><author><style face="normal" font="default" size="100%">Pandreka, Avinash</style></author><author><style face="normal" font="default" size="100%">Kumar, Ashish</style></author><author><style face="normal" font="default" size="100%">Nandikol, Sharvani S.</style></author><author><style face="normal" font="default" size="100%">Haldar, Saikat</style></author><author><style face="normal" font="default" size="100%">Thulasiram, Hirekodathakallu V.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%"> Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension</style></title><secondary-title><style face="normal" font="default" size="100%">BMC Plant Biology</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">18</style></volume><isbn><style face="normal" font="default" size="100%">1471-2229</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Background Neem tree serves as a cornucopia for triterpenoids called limonoids that are of profound interest to humans due to their diverse biological activities. However, the biosynthetic pathway that plant employs for the production of limonoids remains unexplored for this wonder tree.

Results Herein, we report the tracing of limonoid biosynthetic pathway through feeding experiments using C-13 isotopologues of glucose in neem cell suspension. Growth and development specific limonoid spectrum of neem seedling and time dependent limonoid biosynthetic characteristics of cell lines were established. Further to understand the role of mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways in limonoid biosynthesis, Ultra Performance Liquid Chromatography (UPLC)- tandem mass spectrometry based structure-fragment relationship developed for limonoids and their isotopologues have been utilized. Analyses of labeled limonoid extract lead to the identification of signature isoprenoid units involved in azadirachtin and other limonoid biosynthesis, which are found to be formed through mevalonate pathway. This was further confirmed by treatment of cell suspension with mevinolin, a specific inhibitor for MVA pathway, which resulted in drastic decrease in limonoid levels whereas their biosynthesis was unaffected with fosmidomycin mediated plastidial methylerythritol 4-phosphate (MEP) pathway inhibition. This was also conspicuous, as the expression level of genes encoding for the rate-limiting enzyme of MVA pathway, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) was comparatively higher to that of deoxyxylulose-phosphate synthase (DXS) of MEP pathway in different tissues and also in the in vitro grown cells. Thus, this study will give a comprehensive understanding of limonoid biosynthetic pathway with differential contribution of MVA and MEP pathways.

Conclusions Limonoid biosynthesis of neem tree and cell lines have been unraveled through comparative quantification of limonoids with that of neem tree and through C-13 limonoid isotopologues analysis. The undifferentiated cell lines of neem suspension produced a spectrum of C-seco limonoids, similar to parental tissue, kernel. Azadirachtin, a C-seco limonoid is produced in young tender leaves of plant whereas in the hard mature leaves of tree, ring intact limonoid nimocinol accumulates in high level. Furthermore, mevalonate pathway exclusively contributes for isoprene units of limonoids as evidenced through stable isotope labeling and no complementation of MEP pathway was observed with mevalonate pathway dysfunction, using chemical inhibitors.</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">3.930</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mulani, Fayaj A.</style></author><author><style face="normal" font="default" size="100%">Nandikol, Sharvani S.</style></author><author><style face="normal" font="default" size="100%">Haldar, Saikat</style></author><author><style face="normal" font="default" size="100%">Thulasiram, V, Hirekodathakallu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Accurate identification of bioactive meliaceae limonoids by UHPLC-MS/ms based structure-fragment relationships (SFRs)</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Omega</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">26454-26476</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Y Limonoids are bioactive plant specialized metabolites found in the Meliaceae family. The basic limonoids, i.e., azadiradione, epoxyazadiradione, and gedunin have been exploited for various bioactivities and therefore are the potential drug leads for tomorrow. However, their low abundance, structural similarity, and lack of adequate mass fragmentation data have hampered their accurate identification and quantification from various sources. In the present study, basic limonoids such as azadirone, azadiradione, epoxyazadiradione, and gedunin isolated from Neem were utilized for the synthesis of their derivatives and isotopologs. A total of 30 one compounds were used in this study among which five were isolated, two were biotransformed, and 24 were synthesized. Among the synthesized compounds nine are novel compounds including six deuterated analogs/isotopologs which are (1,3-H-2)-1,2dihydro-3 beta-hydroxyazadiradione (9), (1,3,16-H-2)-1,2-dihydro-3 beta-16 beta-dihydroxyazadiradione (10), 3 beta-hydroxyazadiradione (11), 3 beta-16 beta-dihydroxyazadiradione (12), (3-H-2)-3 beta-hydroxyazadiradione (13), (3,16-H-2)-3 beta-16 beta-dihydroxyazadiradione (14), (1,3,7-H-2)-1,2-dihydro-3 beta-hydroxy-7-deacetylazadiradione (15), 1,2,20,21,22,23-hexahydroazadiradione (17), and (1,3-H-2)-1,2-dihydro-3 beta-hydroxygedunin (29). These limonoids along with their semisynthesized derivatives were subjected to ultra high performance liquid chromatography mass spectrometry (UHPLC-MS/MS) and the fragmentation pathway was established based on structure-fragment relationships (SFRs), utilizing high resolution MS/MS data. We have developed a most reliable and easily reproducible protocol describing in depth analysis of SFRs based on the structural modifications and synthesis of isotopologs. Also, the MS/MS fragment library of these basic limonoids generated in this study acts as a fingerprint for accurate identification and quantification of limonoids by MS/MS analysis in various plant tissue extracts, phytopharmaceutical formulations and biological samples.</style></abstract><issue><style face="normal" font="default" size="100%">40</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">3.512</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Jain, Prashant</style></author><author><style face="normal" font="default" size="100%">Shanthamurthy, Chethan D.</style></author><author><style face="normal" font="default" size="100%">Leviatan Ben-Arye, Shani</style></author><author><style face="normal" font="default" size="100%">Yehuda, Sharon</style></author><author><style face="normal" font="default" size="100%">Nandikol, Sharvani S.</style></author><author><style face="normal" font="default" size="100%">Thulasiram, V, Hirekodathakallu</style></author><author><style face="normal" font="default" size="100%">Padler-Karavani, Vered</style></author><author><style face="normal" font="default" size="100%">Kikkeri, Raghavendra</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis</style></title><secondary-title><style face="normal" font="default" size="100%">Chemical Communications</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">APR </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">57</style></volume><pages><style face="normal" font="default" size="100%">3516-3519</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF(165), HB-EGF, and FGF2. Notably, GlcNHAc(6-O-SO3-)-IdoA(2-O-SO3-) (HT-2,6S-NAc) tetrasaccharide showed strong binding with the VEGF(165) growth factor. In vitro vascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF(165) and HT-2,6S-NAc or HT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">28</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;5.996&lt;/p&gt;</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mulani, Fayaj A.</style></author><author><style face="normal" font="default" size="100%">Nandikol, Sharvani S.</style></author><author><style face="normal" font="default" size="100%">Kajjihundi, Jagadeesh S.</style></author><author><style face="normal" font="default" size="100%">Pathappa, Niranjana</style></author><author><style face="normal" font="default" size="100%">Puttappa, Sharanappa</style></author><author><style face="normal" font="default" size="100%">Thulasiram, V. Hirekodathakallu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Ultra-high performance liquid chromatography Q-Orbitrap MS/MS-based profiling and quantification of limonoids in Meliaceae plants</style></title><secondary-title><style face="normal" font="default" size="100%">Analytical and Bioanalytical Chemistry</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">LC-HRMS</style></keyword><keyword><style  face="normal" font="default" size="100%">LC-MS/MS</style></keyword><keyword><style  face="normal" font="default" size="100%">Limonoids</style></keyword><keyword><style  face="normal" font="default" size="100%">Meliaceae</style></keyword><keyword><style  face="normal" font="default" size="100%">Natural product</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantification</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">AUG</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">414</style></volume><pages><style face="normal" font="default" size="100%">6093-6106</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Meliaceae plants have been extensively used in agriculture, folklore, and traditional medicine. They are the major storehouses for structurally diverse limonoids (meliacins) possessing various bioactivities like antifeedant, insecticidal, antimicrobial, etc. However accurate detection of these tetranortriterpenes from the vast pool of metabolites in plant tissue extracts or biological sample is a crucial challenge. Though the mass spectrum (MS) provides the molecular mass and the corresponding elemental composition, it cannot be relied precisely. The exact identification of a specific metabolite demands the MS/MS spectrum containing the signature product ions. In the present study, we have developed the UHPLC Q-Orbitrap-based method for identification, quantification, and characterization of limonoids in different plant tissue extracts requiring minimum plant material. Using this method, we carried out the limonoid profiling in different tissue extracts of sixteen Meliaceae plants and the identification of limonoids was performed by comparing the retention time (RT), ESI-(+)-MS spectrum, and HCD-MS/MS of the purified fifteen limonoids used as reference standards. Our results revealed that early intermediates of the limonoid biosynthetic pathway such as azadiradione, epoxyazadiradione, and gedunin occurred more commonly in Meliaceae plants. The MS/MS spectrum library of the fifteen limonoids generated in this study can be utilized for identification of these limonoids in other plant tissue extracts, botanical fertilizers, agrochemical formulations, and bio pesticides.&lt;/p&gt;
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	Foreign&lt;/p&gt;
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	4.478&lt;/p&gt;
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