Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae)

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74-76

The molecule (6), described as "(2R,3S,4S)-3-hydroxy-4-methyl-2-((11ʹ-phenyl-1ʹ-n-tridecyl) butanolide," should be named "(3S,4R,5S)-4-hydroxy-5-methyl-3-(11’–phenyl-1’-n-undecyl) butanolide."

The molecule (7), described as "(2R,3S,4S)-3-hydroxy-4-methyl-2-(13’ –phenyl-1’-n-undecyl) butanolide," should be named "(3S,4R,5S)-4-hydroxy-5-methyl-3-(13’-phenyl-1’-n-tridecyl) butanolide."

The molecule (6) has been renamed as "(3S,4R,5S)-4-hydroxy-5-methyl-3-(11ʹ-phenyl-1ʹ-n-undecyl)-butanolide," as proposed by the reviewer.

For the same reasons compound (7) was described as "(3S,4R,5S)-4-hydroxy-5-methyl-3-(13ʹ –phenyl-1ʹ-n-tridecyl)- butanolide," as suggested by the reviewer.

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86-89

 “….(Table 1) showed 20 carbon signals…”  In fact, 22 carbon signals are reported subsequently, in lines 87-89.  In addition, the methylene carbon signals reported in both Figs. S1 and S3 should be 7 instead of 9.

Corrected as “….(Table 1) showed 22 carbon signals…”  accordingly, with the 22 carbon signals reported in lines 87-89.  

On Figs. S1 and S3 we can see that the signal at 29.8 is broad than others, suggesting that signals are overlapped. In addition, the low resolution mass spectra was in accord with 22 Carbons

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Fig 1

The diagram of the alkyl chain of the molecule 11b (group R3) should be the same as R3 in 11c. 

Fig 1

The diagram of the alkyl chain R3 of the molecule 11b has been changed as in 11c as shown in red on Fig. 1.

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2.2 In vitro antiplasmodial......

A sentence could be inserted to highlight the synergistic effect that, at least apparently, has the total extract of B. louisii (roots and leaves) with respect to the neutral fraction and alkaloid fraction.

The non-alkaloid fraction of the roots extract and the total extract of leaves of B. louissi was moderately active, while the alkaloid fraction was non-active.

Regarding the leaves, only the total extract showed a moderate activity. In both cases, the synergetic effect of the alkaloid and the non-alkaloid fractions could be evident.

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Compound 1 3 position: The chemical shift is too height. This chemical shift is almost same as 3 position of compound 2, which would not be allylic position.

The attribution of the chemical shift of C-3 in compound 1 was deduced from that of compound 11a where correlations were observed between olefinic protons (H4 and H5) and C-3. This was further confirmed by observing other endiandric acids with the same skeleton and nearly substitution.

Ping‐Shin Yang, Ming‐Jen Cheng, Jih‐Jung Chen, Ih‐Sheng Chen. Two New Endiandric Acid Analogs, a New Benzopyran, and a New Benzenoid from the Root of Beilschmiedia erythrophloia. Helvetica 2008, 91(11), 2130-2138.

Mohamad Nurul Azmi, Charlotte Gény, Aurélie Leverrier, Marc Litaudon, Vincent Dumontet, Nicolas Birlirakis, Françoise Guéritte, Kok Hoong Leong, Siti Nadiah,  Halim, Khalit Mohamad, Khalijah Awang.  Kingianic Acids A–G, Endiandric Acid Analogues from Endiandra kingiana. Molecules 2014, 19(2), 1732-1747; https://doi.org/10.3390/molecules19021732

The solvent, temperature, reaction time of oxidation and esterification should be shown in figure 1.

The solvent, temperature, reaction time of oxidation and esterification are shown in red in Figure 2.

The yield of Dess-Martin oxidation is 70%. The staring material was recovered?

We stopped the reaction when the reaction was almost gone. During the separation by chromatography we were able to recover a very small quantity of the starting material.

Table 5.  The μmol/L should be employed.  The more discussion on the biological activity is required, for example effect of structure, comparison with previous report.

Table 5

The results were expressed in μg/mL for the biological activities of extracts and compounds for homogeneity. Since the biological activity of some mixtures have been evaluated as well.

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28-29

Since abstract is independent part of the paper, the numbers of compounds should be replaced by their chemical names.

Only the names of new derivatives were added. If we add the names of all isolates instead of their numberings, we will exceed the allowed 200 words for the abstract as per the journal.

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 It should be explained why compounds 1-2 and 6-7 have been tested as their mixtures.

Compounds 1-2 are position isomers (double bond) while 6-7 are chain (length) isomers. Both mixtures were showing a single spot on TLC card, indicating their same retardation factor. All the attempts to separate such isomers were unsuccessful independently to the different separation techniques used.

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 Are there any data supporting hypothesis about synergistic action of tested compounds?

Not yet. In fact, compounds 1 and 2 are reported here for the first time. So, it could not be possible to have such hypothesis existing.

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Two individual sentences should not be presented as two separated paragraphs.

Both sentences has been combined to form a paragraph.

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Contribution of the study to clarification of chemotaxonomical relationship of species within the genus Beilschmiedia should be explained.

The Lauraceae family remains the only source of bioactive endiandric acid derivatives. Beilschmiedia and Endiandra genus (Lauraceae) are well known for a long time as a rich source of biologically active secondary metabolites. They are still the only source of this class of secondary metabolites (Lenta et al., 2015). The genus Beilschmiedia is a pantropical genus of about 287 species, only 24 species have been studied phytochemically so far. Endiandric acid derivatives are major constituents of these genus, and are important chemotaxonomic markers used to identify Beilschmiedia plant species from a phytochemical point of view (Wan et al., 2015).

Lenta N.B.; Chouna J.R.; Nkeng-Efouet P.A.; Sewald N. Endiandric acid derivatives and other constituents of plants from the Genera Beilschmiedia and Endiandra (Lauraceae). Biomolecules 2015, 5, 910-942.

Wan M.N.H.W.S.; Wan S.; Farediah A.; Khong H.Y.; Razauden M.Z. A Review on Chemical Constituents and Biological Activities of the Genus Beilschmiedia (Lauraceae). Trop. J. Pharm. Res. 2015, 14 (11), 2139-2150.

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Style of citations should be checked carefully. For example, “Pratiwi et al., 2010 [29]” should be corrected to “Pratiwi et al. [29]”

The reference has been corrected as Pudjastuti et al. [32].

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Delete repeating citation “Makler et al. [30]”.

The repeated reference has been deleted and the remaining one has been corrected as Makler et al. [33]

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In the Materials and Methods section, the provider/producer of equipment used in experiments should clearly be specified (e.g. for Spectramax M3 microplate reader, page, lines).

It has been corrected in the text as follow “was then quantified by Spectramax M3 microplate reader (Abs₆₂₀) from Molecular Devices LLC.”

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Both sentences are starting with expression “In addition”. Modify it.

Corrected as

“In addition, four new derivatives (11a, 11b, 11c, and 11d) were synthesized from compound 11. Furthermore, the isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the P. falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively.”