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-002641nas a2200289 4500008004100000245015100041210006900192260000800261300001100269490000700280520161900287653001501906653002201921653002101943653002501964653002801989653001802017100002402035700002702059700002202086700002102108700002402129700002302153700002402176700002302200856012802223 2022 eng d00aDiversity assessment of Gloriosa superba accessions from Western Ghats of India based on morphological traits, ISSR markers and metabolite content0 aDiversity assessment of Gloriosa superba accessions from Western cSEP a1003880 v303 a

Gloriosa superba L. (glory lily) is a medicinally and horticulturally important plant used as a commercial source of the alkaloid colchicine. The Western Ghats in India is mostly unexplored for the morphological, genetic, and metabolite diversity of the species. In the current study, three methodologies were employed to assess the diversity among 50 established accessions of G. superba collected from several locations in the Western Ghats. The morphological analysis revealed that, among the studied traits, seed yield per vine and dry seed weight per 100 seeds for the established accessions were the most diverse traits. The former exhibited a significantly positive correlation with four vegetative and five yield traits. The first three principal components showed nine traits contributing to the variation. Intra-specific molecular variation based on inter simple sequence repeat markers distributed the accessions in three clusters with high polymorphism and low genetic diversity indices. Liquid chromatography high-resolution mass spectrometry analysis revealed significant variation among the screened accessions for colchicine content in tuber and seed tissue. Interestingly, an unexplored tissue, pod shell, was found to contain significantly high colchicine, which could be explored for commercial colchicine extraction. The morphogenetic and metabolite variation revealed by the study would be useful to develop elite varieties to expand the cultivation of glory lily across the country, fulfilling the increasing demand for colchicine and providing remunerative income to the farmers.

10aColchicine10aGenetic diversity10aGloriosa superba10aMetabolite diversity10aMorphological diversity10aWestern Ghats1 aMahajan, Yogesh, A.1 aShinde, Balkrishna, A.1 aMulani, Fayaj, A.1 aGade, Akshay, B.1 aKasodekar, Amol, K.1 aThulasiram, H., V.1 aKadoo, Narendra, Y.1 aNikam, Tukaram, D. uhttps://library.ncl.res.in/content/diversity-assessment-gloriosa-superba-accessions-western-ghats-india-based-morphological02422nas a2200301 4500008004100000022001400041245011200055210006900167260000800236300001100244490000800255520141300263653002501676653001501701653002201716653001501738653002701753653002101780100002401801700002701825700002401852700002001876700002701896700002401923700002401947700002301971856012601994 2024 eng d a0926-669000aUnlocking the genetic and biotechnological potential of Gloriosa superba to enhance its alkaloid production0 aUnlocking the genetic and biotechnological potential of Gloriosa cMAY a1181440 v2113 a

Gloriosa superba is a medicinally important plant that produces the pharmaceutically precious colchicine molecule. Colchicine is being used for treating gout, for enhancing the production of interleukin-8 (inhibits human pancreatic cancer) and many other human ailments. Since its seeds and rhizomes (tuberous roots) are the chief sources of colchicine, pharmaceutical industries exploit the natural sources, thus demolishing its habitat. Chemo- and genetic diversity among the G. superba populations exist, but has not been exploited profitably. Scope exists for generating mutants using the chemical mutagens and also via breeding methods to generate superior varieties for commercial cultivation. Innovative methods for breaking seed dormancy and superior colchicine extraction, besides biotechnological interventions are imperative to save the biodiversity and to produce colchicine on a large scale. Biorhizomes produced in vitro hold great promise for biomanufacturing colchicine in bioreactors commercially. Since the biosynthetic pathway of colchicine is now known, isolation of the pathway genes and their heterologous overexpression or the application of synthetic biology methods needs to be explored in future for industrial manufacturing of colchicine. Advances made in the recent past in these fields of colchicine production from G. superba are critically evaluated in this review.

10aBiosynthetic pathway10aColchicine10aGenetic diversity10aGlory lily10aMetabolite elicitation10aOmics approaches1 aMahajan, Yogesh, A.1 aShinde, Balkrishna, A.1 aShirke, Harshad, A.1 aGandra, Jawahar1 aSuravajhala, Prashanth1 aKishor, P., B. Kavi1 aKadoo, Narendra, Y.1 aNikam, Tukaram, D. uhttps://library.ncl.res.in/content/unlocking-genetic-and-biotechnological-potential-gloriosa-superba-enhance-its-alkaloid