01682nas a2200217 4500008004100000022001400041245014000055210006900195260007500264300001200339490000600351520083800357653001801195653001501213653001601228653001301244653002601257100002401283700002801307856012901335 2016 eng d a2193-580700aDiastereoselective synthesis of beta-ether derivatives of artemisinin, an antimalarial drug: the effect of nitrile on stereoselectivity0 aDiastereoselective synthesis of betaether derivatives of artemis aPOSTFACH 101161, 69451 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcFEB a201-2060 v53 a

Malaria is a life-threatening disease affecting a major portion of the world's population with considerable loss of human life. Artemisinin, isolated from Artemisia annua, its oil- and water-soluble derivatives, and other known antimalarials are recommended for artemisinin combination therapy by the World Health Organization. We have established a method for the stereoselective synthesis of beta-ether derivatives of dihydroartemisinin in high yield and high diastereoselectivity. The reaction either in acetonitrile or dichloromethane/trichloroacetonitrile (6:1) mixtures at 0 degrees C or room temperature, respectively, furnished the antimalarial drugs artemether 3 or arteether 4 in high yield with a high diastereomeric ratio. The effect the nitrile has on the yield and stereoselectivity is mechanistically explained.

10aantimalarials10aarteethers10aartemisinin10anitriles10atrichloroacetimidates1 aChand, Hemender, R.1 aBhattacharya, Asish, K. uhttp://library.ncl.res.in/content/diastereoselective-synthesis-beta-ether-derivatives-artemisinin-antimalarial-drug-effect-001959nas a2200301 4500008004100000022001400041245004800055210004700103260000900150490000700159520111600166653001601282653001601298653002201314653001201336653001501348653001501363653000601378100002401384700002401408700001701432700002601449700002601475700001801501700002801519700002801547856008201575 2023 eng d a1860-717900aHistidinal-based potent antimalarial agents0 aHistidinalbased potent antimalarial agents cMAY 0 v183 a

Herein we report the synthesis and evaluation of peptide-histidinal conjugated drug scaffolds, which have the potential to target the hemoglobin-degrading proteases falcipain-2/3 from the human malaria parasite. Scaffolds with various substitutions were tested for antimalarial activity, and compounds 8 g, 8 h, and 15 exhibited EC50 values of similar to 0.018 mu M, similar to 0.069 mu M, and similar to 0.02 mu M, respectively. Structure-based docking studies on falcipain-2/3 proteases (PDB:2GHU and PDB:3BWK) revealed that compounds 8 g, 8 h, and 15 interact strongly with binding sites of falcipain-2/3 in a substrate-like manner. In silico ADME studies revealed that the molecules of interest showed no or minimal violations of drug-likeness parameters. Further, phenotypic assays revealed that compound 8 g and its biotinylated version inhibit hemoglobin degradation in the parasite food vacuole. The identification of falcipain-2/3 targeting potent inhibitors of the malaria parasite can serve as a starting point for the development of lead compounds as future antimalarial drug candidates.

10aartemisinin10achloroquine10adigestive vacuole10adocking10afalcipains10afalciparum10aP1 aMeena, Chhuttan, L.1 aHingamire, Tejashri1 aGupta, Tanya1 aDeshmukh, Bhagyashree1 aKarmodiya, Krishanpal1 aJoshi, Rakesh1 aShanmugam, Dhanasekaran1 aSanjayan, Gangadhar, J. uhttp://library.ncl.res.in/content/histidinal-based-potent-antimalarial-agents02224nas a2200241 4500008004100000022001400041245010200055210006900157260000800226490000800234520137900242653001601621653001301637653002001650653002001670100001801690700002901708700002801737700002401765700002701789700003601816856013001852 2023 eng d a0927-776500aInhibitory effect of curcumin-artemisinin co-amorphous on Tau aggregation and Tau phosphorylation0 aInhibitory effect of curcuminartemisinin coamorphous on Tau aggr cJAN0 v2213 a

Tau is a natively unfolded microtubule-associated protein. Tau neurofibrillary tangles are one of the hallmarks of Alzheimer's disease. The post-translational modifications of Tau lead to its pathological state. Phosphorylation is the key post-translational modification associated with Tauopathy. Curcumin is a polyphenolic compound pre-sent in the rhizomes of Curcuma longa. Curcumin has been reported to have remarkable medicinal properties in several diseases, but its poor solubility limits its therapeutic potency. Artemisinin is a sesquiterpene lactone, which has been known sience ancient times for its applications as a treatment for various diseases such as malaria, cancer, autoimmune disease, etc. In the present study, the potency of crystalline curcumin, crystalline artemisinin, and Cur-Art co-amorphous dispersion were evaluated against Tau pathology. The in-vitro ThS/ANS fluorescence and electron microscopy results suggested that curcumin and Cur-Art efficiently inhibited Tau aggregation. Furthermore, exposure to curcumin and Cur-Art co-amorphous restored the impaired nuclear transport in formaldehyde-stressed cells. Curcumin was also found to modulate the phosphorylation of Tau, which indicated the neuroprotective potency. Thus, curcumin and Cur-Art co-amorphous exhibit therapeutic potential against Tau protein in Alzheimer's disease.

10aartemisinin10acurcumin10aPhosphorylation10aTau Aggregation1 aDubey, Tushar1 aSonawane, Shweta, Kishor1 aMannava, M., K. Chaitan1 aNangia, Ashwini, K.1 aChandrashekar, Madhura1 aChinnathambi, Subashchandrabose uhttp://library.ncl.res.in/content/inhibitory-effect-curcumin-artemisinin-co-amorphous-tau-aggregation-and-tau-phosphorylation02114nas a2200217 4500008004100000022001400041245016000055210006900215260000900284490000700293520129800300653001701598653002101615653001601636653002601652653001701678100001901695700002701714700003101741856012401772 2023 eng d a1861-472800aLate-stage C(sp(2))-H arylation of artemisinic acid and arteannuin B: effect of olefin migration towards synthesis of C-13 arylated artemisinin derivatives0 aLatestage Csp2H arylation of artemisinic acid and arteannuin B e cAPR 0 v183 a

In recent years, C-H bond functionalization has emerged as a pivotal tool for late-stage functionalization of complex natural products for the synthesis of potent biologically active derivatives. Artemisinin and its C-12 functionalized semi-synthetic derivatives are well-known clinically used anti-malarial drugs due to the presence of the essential 1,2,4-trioxane pharmacophore. However, in the wake of parasite developing resistance against artemisinin-based drugs, we conceptualized the synthesis of C-13 functionalized artemisinin derivatives as new antimalarials. In this regard, we envisaged that artemisinic acid could be a suitable precursor for the synthesis of C-13 functionalized artemisinin derivatives. Herein, we report C-13 arylation of artemisinic acid, a sesquiterpene acid and our attempts towards synthesis of C-13 arylated artemisinin derivatives. However, all our efforts resulted in the formation of a novel ring-contracted rearranged product. Additionally, we have extended our developed protocol for C-13 arylation of arteannuin B, a sesquiterpene lactone epoxide considered to be the biogenetic precursor of artemisinic acid. Indeed, the synthesis of C-13 arylated arteannuin B renders our developed protocol to be effective in sesquiterpene lactone as well.

10aArteannuin B10aArtemisinic acid10aartemisinin10aC-H functionalization10aPd-catalysis1 aPaul, Sayantan1 aGhodake, Balaji, M. M.1 aBhattacharya, Asish, K. K. uhttp://library.ncl.res.in/content/late-stage-csp2-h-arylation-artemisinic-acid-and-arteannuin-b-effect-olefin-migration