01047nas a2200181 4500008004100000022001400041245008100055210006900136260000900205300001400214490000700228520042500235100002100660700001900681700002800700700002800728856010900756 2019 eng d a1144-054600aSynthesis of artemisinin derived glycoconjugates inspired by click chemistry0 aSynthesis of artemisinin derived glycoconjugates inspired by cli cMAR  a4017-40210 v433 a

Herein we describe the synthesis of artemisinin based glycoconjugates (9a-i) through employing a Cu(i)-catalysed reaction between -propargylated dihydroartemisinin (7a) and azido sugars (8a-i), with moderate to excellent yields. Our synthesized artemisinin based glycoconjugates (9a-i) could prove to be an interesting class of bioactive molecules, suitable for the study of their various biological activities.

1 aGoswami, Lakshmi1 aPaul, Sayantan1 aKotammagari, Tharun, K.1 aBhattacharya, Asish, K. uhttp://library.ncl.res.in/content/synthesis-artemisinin-derived-glycoconjugates-inspired-click-chemistry02280nas a2200193 4500008004100000245013400041210006900175260000800244300001200252490000700264520155200271100002101823700001801844700001901862700002001881700002601901700002801927856013101955 2022 eng d00aDesign and synthesis of eugenol/isoeugenol glycoconjugates and other analogues as antifungal agents against Aspergillus fumigatus0 aDesign and synthesis of eugenolisoeugenol glycoconjugates and ot cAUG a955-9620 v133 a

Glycoconjugates are biologically significant molecules as they tend to serve a wide range of intra- and extra-cellular processes depending on their size and complexity. The secondary metabolites of the plant Myristica fragrans, eugenol and isoeugenol, have shown antifungal activities (IC50 1900 mu M). Therefore, we envisioned that glycoconjugates based on these two scaffolds could prove to be potent antifungal agents. Triazole-containing compounds have shown prominent activities as antifungal agents. Based on this, we opined that a Cu(i) catalyzed click reaction could serve as the bridging tool between a eugenol/isoeugenol moiety and sugars to synthesize eugenol/isoeugenol based glycoconjugates. In our present work, we have coupled propargylated eugenol/isoeugenol and azido sugar to furnish eugenol/isoeugenol based glycoconjugates. In another approach, we have carried out hydroxylation of the double bond of eugenol and subsequent azidation of a primary alcohol followed by intramolecular coupling reactions leading to various other analogues. All the synthesized compounds were assayed against an opportunistic pathogenic fungus, Aspergillus fumigatus. Among the synthesized compounds, two analogues have exhibited significant antifungal activities with IC50 values of 5.42 and 9.39 mu M, respectively. The study suggested that these two analogues inhibit cell wall-associated melanin hydrophobicity along with the number of conidia. The synthesized compounds were found to be non-cytotoxic to an untransformed cell line.

1 aGoswami, Lakshmi1 aGupta, Lovely1 aPaul, Sayantan1 aVermani, Maansi1 aVijayaraghavan, Pooja1 aBhattacharya, Asish, K. uhttp://library.ncl.res.in/content/design-and-synthesis-eugenolisoeugenol-glycoconjugates-and-other-analogues-antifungal-agents02317nas a2200253 4500008004100000022001400041245009700055210006900152260000900221490000700230520148500237653000601722653001301728653002201741653002601763653002301789653001501812100002101827700001801848700001901866700002601885700002801911856012401939 2023 eng d a1860-717900aDesign and synthesis of 1,3-diynes as potent antifungal agents against aspergillus fumigatus0 aDesign and synthesis of 13diynes as potent antifungal agents aga cMAY 0 v183 a

Eugenol and isoeugenol, secondary metabolites isolated from the plant Myristica fragrans have displayed antifungal activities against Aspergillus fumigatus (IC50 1900 mu M). Compounds having conjugated unsaturation have been of great use as antifungals i. e. amphotericin B, nystatin and terbinafine etc. Hence, in the present study, we have designed and synthesised 1,3-diynes by utilizing Glaser-Hay and Cadiot-Chodkiewicz coupling reactions to furnish possible antifungal agents. Synthesis of 1,6-diphenoxyhexa-2,4-diyne derivatives was achieved by Cu(I) catalysed coupling of propargylated eugenol, isoeugenol, guaiacol, vanillin and dihydrogenated eugenol or eugenol in good to excellent yields. All the synthesized compounds were evaluated against pathogenic fungus A. fumigatus. Among all the synthesized compounds, one of the compounds was found to be exhibiting promising antifungal activity with IC50 value of 7.75 mu M thereby suggesting that this type of scaffold could pave the way for developing new antifungal agents. The most active compound was found to be low cytotoxic when assayed against L-132 cancer cell line. Effect of the most active compound on ergosterol biosynthesis has also been studied. Also, the most active compound exhibited significant anti-biofilm activity although the concentration was found to be higher than its anti-fungal activity. Morphological changes in the biofilm were remarkable under confocal laser scanning microscopy.

10a110a3-Diynes10aAntifungal agents10aAspergillus fumigatus10aCadiot-Chodkiewicz10aGlaser-Hay1 aGoswami, Lakshmi1 aGupta, Lovely1 aPaul, Sayantan1 aVijayaraghavan, Pooja1 aBhattacharya, Asish, K. uhttp://library.ncl.res.in/content/design-and-synthesis-13-diynes-potent-antifungal-agents-against-aspergillus-fumigatus01935nas a2200241 4500008004100000022001400041245014800055210006900203260000800272490000700280520105400287653003201341653003001373653002501403653001201428653001501440100002101455700001901476700002101495700002401516700002801540856012501568 2024 eng d a2193-580700aMethanesulfonic acid-catalyzed friedel-crafts alkylation: towards sustainable synthesis of arylalkanes from donor-acceptor cyclopropane ketones0 aMethanesulfonic acidcatalyzed friedelcrafts alkylation towards s cJUL0 v133 a

We present herein Br & oslash;nsted acid-catalyzed Friedel-Crafts alkylation of phenols with Donor-Acceptor cyclopropane ketones. The presence of the 1,4-diphenyl butan-1-one and 1,3-diphenyl propane-1-one motifs in various naturally occurring biologically significant molecules inspired us to pursue the direct synthesis of these structural frameworks. Utilizing methanesulfonic acid (MeSO3H) as a catalyst, we achieved a more environmentally friendly and high-yielding synthesis, owing to its cost-effectiveness, biodegradability, transition-metal and additives free conditions. Furthermore, we have successfully extended our developed methodology to thiophenols, resulting in the production of sulfur-based butan-1-one derivatives in good yields. The presence of 1,4-diphenyl butan-1-one and 1,3-diphenyl propane-1-one motifs in various naturally occurring biologically significant molecules prompted us to develop a Br & oslash;nsted acid-catalyzed Friedel-Crafts alkylation of phenols with Donor-Acceptor cyclopropane. image

10adonor-acceptor cyclopropane10aFriedel-Crafts alkylation10amethanesulfonic acid10aPhenols10athiophenol1 aGoswami, Lakshmi1 aPaul, Sayantan1 aMamale, Ajay, G.1 aGonnade, Rajesh, G.1 aBhattacharya, Asish, K. uhttp://library.ncl.res.in/content/methanesulfonic-acid-catalyzed-friedel-crafts-alkylation-towards-sustainable-synthesis02990nas a2200277 4500008004100000022001400041245018800055210006900243260000900312490000800321520198600329653002602315653002402341653001202365653001902377653002902396653001402425100001802439700001902457700002102476700002102497700001502518700002802533700002602561856012502587 2024 eng d a1364-507200aUnveiling the cell wall-targeting mechanisms and multifaceted virulence modulation by a eugenol glycoconjugate against aspergillus fumigatus: insights from in vitro and in ovo studies0 aUnveiling the cell walltargeting mechanisms and multifaceted vir cJAN 0 v1353 a

Aim The primary objective of this study was to elucidate the putative cell wall-associated targets of compound 6i, a glycoconjugate of eugenol, in Aspergillus fumigatus, while also evaluating its toxicity and assessing histopathologic alterations in the liver, heart, and kidney of compound 6i-treated embryos using an in ovo model.Method To achieve this aim, compound 6i was synthesized, and a series of biochemical assays were performed to determine its impact on the fungal cell wall. Additionally, quantitative real time-PCR and liquid chromatography-mass spectrometry/mass spectrometry analyses were conducted to investigate changes in gene and protein expression profiles associated with melanin biosynthesis, conidiation, siderophore production, transcriptional regulation of beta-glucan biosynthesis, and calcineurin activity in A. fumigatus.Results The experimental findings revealed that compound 6i exhibited notable antifungal activity against A. fumigatus by perturbing cell wall integrity, hindering ergosterol, glucan, and chitin biosynthesis, and inhibiting catalase production. Moreover, relative gene expression and proteomic analyses demonstrated that compound 6i exerted both downregulatory and upregulatory effects on several crucial genes and proteins involved in the aforementioned fungal processes. Furthermore, increased expression of oxidative stress-related proteins was observed in the presence of compound 6i. Notably, the glycoconjugate of eugenol did not elicit cytotoxicity in the liver, heart, and kidney of chick embryos.Conclusion The current investigation elucidated the multifaceted mechanisms by which compound 6i exerts its antifungal effects against A. fumigatus, primarily through targeting cell wall components and signaling pathways. These findings underscore the potential of the eugenol glycoconjugate as a promising antifungal candidate, warranting further exploration and development for combating A. fumigatus infections.

10aAspergillus fumigatus10acell wall integrity10aEugenol10aGlycoconjugate10aTranscription regulators10aVirulence1 aGupta, Lovely1 aVerma, Shalini1 aGoswami, Lakshmi1 aKamboj, Himanshu1 aSen, Pooja1 aBhattacharya, Asish, K.1 aVijayaraghavan, Pooja uhttp://library.ncl.res.in/content/unveiling-cell-wall-targeting-mechanisms-and-multifaceted-virulence-modulation-eugenol