Natural Whole plants Euphorbia hirta Leaves Fabaceae Leucaena

Topic: LifeDream
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Last updated: August 23, 2019

Naturalplants: There are many plants whose extracts showanti-dengue property. Carica papaya isa very common plant whose leaf extract is used in this disease.

It was used ina mid-age patient where it was found that 5 days treatment of the extract ledto increase in WBC as well as platelet count. Other plants extracts which havesignificant role in the treatment of dengue are listed in the table below.Table 1 List of plants whose extracts havebeen used in dengue. Family Species Part(s) used Compound isolated Acanthaceae Andrographis paniculata Leaves   Amaranthaceae Alternanthera philoxeroides       Whole plants   Caricaceae Carica papaya Leaves   Chordariaceae Cladosiphon okamuranus Whole plants Fucoidan Cucurbitacea Momordica charanthia Fruit   Elaeagnaceae Hippophae rhamnoides Leaves   Euphorbiaceae Cladogynos orientalis Whole plants     Euphorbia hirta Leaves   Fabaceae Leucaena leucocephala Seeds Galactomanan   Mimosa scabrella Seeds Galactomanan   Tephrosia madrensis Leaves and flowers Glabranine   Tephrosia crassifolia Leaves and flowers     Tephrosia viridiflora Leaves and flowers   Fagaceae Quercus lusitanica Seeds   Flagellariaceae Flagellaria  indica Whole plants   Halymeniaceae Cryptonemia crenulata Whole plants Galactan Labiatae Ocimum sanctum Leaves   Meliaceae Azidarachta indica Leaves   Myrtaceae Psidium guajava Leaves   Piperaceae Piper retrofractum Whole plants   Phyllophoraceae Gymnogongrus torulosus Whole plants Galactan   Gymnogongrus griffithsiae Whole plants Kappa carrageenan Poaceae Cymbopogon citratus Whole plants   Rhizophoraceae Rhizophora apiculata Whole plants   Rubiaceae Uncaria tomentosa Stem barks   Saururaceae Houttuynia cordata Whole plants Hyperosid Solieriaceae Meristiella gelidium Whole plants Kappa carrageenan Verbenaceae Lippia alba Whole plants     Lippia citriodora Whole plants     Leucaena leucocephalaleaves contain galactomannans which has been tested in vivo for the activitiesagainst yellow fever virus and DENV-1. Apart from that Azadiracta indica has also shown significant role in vivo in inhibiting the replication ofDENV-2.  Naturalchemical moieties against dengue:There are many naturalcompounds which have shown significant activity against dengue. They belong todifferent chemical classes like sulfated polysaccharides, flavonoids, quercetin,natural chalcone compounds etc. Here are some of the active anti-dengue naturalcompounds:SARof some important compounds against NS2b-NS3:SARof methionine–proline anilides:Two methionine–proline anilides have been found toinhibit NS2b-NS3efficiently.

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Their Kivalues are found to be 4.9 and 10.5 respectively. Table 2 Chemical structures of dipeptides and their activitiesagainst DENV 2 NS2B-NS3 protease. Sr. No. R X Z Ki  (µM) Remaining activity of DENV 2 NS2B-NS3 1 4-NO2 H S 4.9 31%   2 4-NO2 Boc S 10.

5 45%   3 3-NO2 H S   37%   4 2-NO2 H S   96%   5 H H S   60%   6 4-NO2 H S   36%   7 H H S   58%   8 4-NO2 H S(O)   71%   9 4-NO2 H S(O)2   99%   10 4-NO2 H S   103%   11 4-NO2 CF3CO S   54%   12 4-NO2 No2-Bn S   38%   13 4-NO2 MeO-Bn S   90%    1.      X=H2.      X=Boc As it can be seenclearly from the table that no significant change in activity is found if the Sat Z is replaced by S(O)2 but activity got decreased upto 45% when Xgroup was replaced by Boc but replacement with H gave the most potent compoundwhich decreased the activity for upto 31%. Further if methionine is replaced byphenylalanine, the activity remains only upto 25% but it has higher inhibitoryconcentration (200 µM).

SARof tetrapeptide aldehyde inhibitors:They started with the following aldehyde derivative(Ki =5.8 µM) to determinethe pharmacophoric features of the NS3 active site.Figure 1 A tetrapetide aldehyde derivativeTable 3 Results from different scans (alanine, phenylalanine,lysine, and proline, D- and N-Me amino acids) and varying the inhibitor Sr. No. Aldehyde inhibitors Ki (µM) 1 Bz-Nle-Lys-Arg-Arg-H 5.

8 2 Bz-Nle-Lys-Arg-Ala-H 193.0 3 Bz-Nle-Lys-Ala-Arg-H >500 4 Bz-Nle-Ala-Arg-Arg-H 22.1 5 Bz-Ala-Lys-Arg-Arg-H 5.3 6 Bz-Nle-Lys-Arg-Phe-H 15.9 7 Bz-Nle-Lys-Phe-Arg-H 40.7 8 Bz-Nle-Phe-Arg-Arg-H 15.

8 9 Bz-Phe-Lys-Arg-Arg-H 6.8 10 Bz-Nle-Lys-Arg-Lys-H 20.5 11 Bz-Nle-Lys-Lys-Arg-H 41.3 12 Bz-Nle-Lys-Pro-Arg-H 109.

0 13 Bz-Nle-Pro-Arg-Arg-H 61.4 14 Bz-Nle-Lys-N-Me-Arg-Arg-H 47.4 15 Bz-Nle-N-Me-Lys-Arg-Arg-H 113.3 16 Bz-N-Me-Nle-Lys-Arg-Arg-H 43.7 17 Bz-Nle-Lys-Arg-D-Arg-H 51.

0 18 Bz-Nle-Lys-D-Arg-Arg-H 115.0 19 Bz-Nle-D-Lys-Arg-Arg-H 28.6 20 Bz-D-Nle-Lys-Arg-Arg-H 9.4 21 Bz-Lys-Arg-Arg-H 1.5 22 Bz-Arg-Arg-H 12.

0 23 Bz-Nle-Lys-Arg-(p-guanidinyl)Phe-H 2.8  When they replaced Arg atP1 with Lys, They found that the activity of the inhibitor was increased fourtimes but the activity increased eight fold when they replaced Arg at P2. Themost potent compound was obtained when P1 was replaced with (p-guanidinyl)Phe with Ki = 2.8 µM. When P2 and P3 were replacedwith proline a huge loss in activity was found which indicated that turngeometry was unfavourable in binding.            Replacement of P1 gave some active compound but the Ki is not that much good.

Themost effective replacement at P1 was fount to be Trp which gave compound with  Ki=7.5µM.Table 4 Effect of modifications in the P1 position of thetetrapeptide P1 Ki (µM) Phe 15.9 Phg 33.0 homoPhe >500 (p-Cl)Phe 138.0 (p-CN)Phe 18.6 (p-Me)Phe 6.0 (p-Ph)Phe 11.6 Trp 7.5  Phe alone at P1 gave lesserpotent compound as compared to the compound which was obtained by replacing P1with -(p-guanidinyl)Phe.

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