01752nas a2200169 4500008004100000245017100041210006900212260000800281300001200289490000600301520106100307100002401368700002401392700001901416700002801435856011901463 2016 eng d00aNaturally occurring anti-TB agents: isolation, chemical transformations and in vitro antitubercular activities of secondary metabolites of rhizomes of alpinia galanga0 aNaturally occurring antiTB agents isolation chemical transformat cSEP ae55-e590 v33 a

A bioactivity-guided chemical examination of the acetone extract of the rhizomes of Alpinia galanga led to the isolation of six sec-ondary metabolites, eucalyptol derivative (1)andphenylpropa-noids (2–6). The structures of all of the isolated compounds (1–6)wereelucidatedonthebasisoftheirspectraldata.Theisolatedcompounds (1–6)werein vitro assayed against active and dor-mant phenotypes of Mycobacterium tuberculosis H37Ra, respec-tively. Interestingly, 1′S-1′-acetoxychavicol acetate (2)showedgood antitubercular activities against both active and dormantphenotypes of M. tuberculosis with IC50 values of 1.04 µM and2.69 µM, respectively. Tsuji-Trost and homodimerization reac-tions of the active compound (2)respectivelyresultedinthefor-mation of two analogues, 7and 8.Bothofthesesynthesizedana-logues were also found to be active in vitro against active [IC50 sof3.24 and 3.87 µM, respectively, for compounds 7and 8]anddor-mant [IC50 sof8.33and2.41µM,respectively,forcompounds7and 8]phenotypesofM. tuberculosis H37Ra, respectively.

1 aValkute, Tushar, R.1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/naturally-occurring-anti-tb-agents-isolation-chemical-transformations-and-vitro03665nas a2200193 4500008004100000022001400041245017700055210006900232260000800301300001400309490000800323520288800331100002603219700002403245700002003269700002303289700002803312856013103340 2017 eng d a0223-523400aNorepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents0 aNorepinephrine alkaloids as antiplasmodial agents Synthesis of s cSEP a1089-11050 v1383 a

Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 mu M (D6 clone), 3.06 mu M (W2 clone) and observed by us 3.90 mu M (3D7 clone) and 2.56 mu M (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3-57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 mu M (3D7) and 1.78, 2.07 mu M (I(1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 mu M against 3D7 strain, 4.27, 7.26, 2.71 mu M against K1 strain and with CC50 values of 147.72, 153.0, >200 mu M respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1: The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chioroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 mu M, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin. (C) 2017 Elsevier Masson SAS. All rights reserved.

1 aAratikatla, Eswar, K.1 aValkute, Tushar, R.1 aPuri, Sunil, K.1 aSrivastava, Kumkum1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/norepinephrine-alkaloids-antiplasmodial-agents-synthesis-syncarpamide-and-insight-structure