scholarly journals Digyaindoleacid A: 2-(1-(4-Hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic Acid, a Novel Indole Alkaloid

Molbank ◽  
10.3390/m1080 ◽  
2019 ◽  
Vol 2019 (3) ◽  
pp. M1080 ◽  
Author(s):  
Samuel Kwain ◽  
Gilbert Tetevi ◽  
Thomas Mensah ◽  
Anil Camas ◽  
Mustafa Camas ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Donovani ◽  
Indole Alkaloid ◽  
2D Nmr ◽  
The Novel ◽  
Diminazene Aceturate ◽  
Paenibacillus Sp ◽  
Mouse Macrophages ◽  
Low Toxicity ◽  
Uptake And Metabolism

Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 μM compared to the standard diminazene aceturate (IC50 = 1.86 μM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain GUTat 3.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 μM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

scholarly journals Paenidigyamycin G: 1-Acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium

Molbank ◽  
10.3390/m1094 ◽  
2019 ◽  
Vol 2019 (4) ◽  
pp. M1094
Author(s):  
Gilbert Mawuli Tetevi ◽  
Samuel Kwain ◽  
Thomas Mensah ◽  
Anil Sazak Camas ◽  
Mustafa Camas ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Parent Compound ◽  
2D Nmr ◽  
Culture Broth ◽  
Raw 264.7 Cells ◽  
Antiparasitic Activity ◽  
Paenibacillus Sp ◽  
Mouse Macrophages ◽  
Low Toxicity ◽  
Activity Screening

The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 μM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

scholarly journals First Total Synthesis of ω-Phenyl Δ6 Fatty Acids and their Leishmanicidal and Anticancer Properties

2018 ◽  
Vol 18 (5) ◽  
pp. 418-427 ◽  
Author(s):  
Nestor M. Carballeira ◽  
Christian Morales-Guzman ◽  
Ester Alvarez-Benedicto ◽  
Zally Torres-Martinez ◽  
Yamixa Delgado ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Total Synthesis ◽  
Leishmania Donovani ◽  
A549 Cells ◽  
The Novel ◽  
Murine Splenocytes ◽  
Anticancer Properties ◽  
Topoisomerase Ib ◽  
Low Toxicity ◽  
Induced Apoptosis

Introduction: The first total synthesis of ω-phenyl Δ6 fatty acids (FA) and their cytotoxicity (A549) and leishmanicidal (L. infantum) activities are described. The novel 16-phenyl-6-hexadecynoic acid (1) and the known 16-phenylhexadecanoic acid (2) were synthesized in 7-8 steps with overall yields of 46 % and 41 %, respectively. The syntheses of the unprecedented 10-phenyl-6-decynoic acid (3), 10-cyclohexyl-6-decynoic acid (4) and 10-(4-methoxyphenyl)-6-decynoic acid (5) was also performed in 3 steps with 73-76 % overall yields. The use of lithium acetylide coupling enabled the 4-step synthesis of 10-phenyl-6Z-decenoic acid (6) with a 100 % cis-stereochemistry. The cytotoxicity of these novel FA was determined against A549 cells and L. infantum promastigotes and amastigotes. Among the ω-phenylated FA, the best cytotoxicity towards A549 was displayed by 1, with an IC50 of 18 ± 1 μM. On the other hand, among the C10 acids, the ω-cyclohexyl acid 4 presented the best cytotoxicity (IC50 = 40 ± 2 μM) towards A549. Results: Based on caspase-3/7 studies neither of the FA induced apoptosis in A549, thus implying other mechanisms of cell death. Conclusion: The antileishmanial studies were performed with the top Leishmania donovani topoisomerase IB (LdTopIB) inhibitors, namely 1 and 2 (EC50 between 14 and 36 μM, respectively), acids that did not stabilize the cleavage complexes between LdTopIB and DNA. Acids 1 and 2 displayed cytotoxicity towards L. infantum amastigotes (IC50 = 3-6 μM) and L. infantum promastigotes (IC50 = 60- 70 μM), but low toxicity towards murine splenocytes. Our results identified 1 as the optimum ω- phenylated acid of the series.

scholarly journals Anthocephaline, a New Indole Alkaloid and Cadambine, a Potent Inhibitor of DNA Topoisomerase IB of Leishmania donovani (LdTOP1LS), Isolated from Anthocephalus cadamba

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000
Author(s):  
Ashish Kumar ◽  
Somenath Roy Chowdhury ◽  
Kumar Kalyan Jatte ◽  
Tulika Chakrabarti ◽  
Hemanta K Majumder ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Inhibitory Activity ◽  
Leishmania Donovani ◽  
Potent Inhibitor ◽  
Indole Alkaloid ◽  
2D Nmr ◽  
Stem Bark ◽  
Dna Topoisomerase ◽  
Topoisomerase Ib ◽  
Anthocephalus Cadamba

Chemical investigation of the stem bark of Anthocephalus cadamba has resulted in the isolation of anthocephaline (1), a new indole alkaloid, along with strictosamide (2), vincosamide (3) and cadambine (4). The structures of the isolated alkaloids (1-4) were established by detailed 2D NMR spectral analysis. Cadambine (4) exhibited potent DNA topoisomerase IB inhibitory activity.

scholarly journals Paenidigyamycin A, Potent Antiparasitic Imidazole Alkaloid from the Ghanaian Paenibacillus sp. DE2SH

Marine Drugs ◽  
2018 ◽  
Vol 17 (1) ◽  
pp. 9 ◽  
Author(s):  
Enoch Osei ◽  
Samuel Kwain ◽  
Gilbert Mawuli ◽  
Abraham Anang ◽  
Kofi Owusu ◽  
...  
Keyword(s):  
Amphotericin B ◽  
National Park ◽  
2D Nmr ◽  
The Novel ◽  
Nmr Data ◽  
Coptis Japonica ◽  
Paenibacillus Sp ◽  
Minimal Effective Concentration ◽  
Pterocarpus Santalinoides ◽  
Minimal Lethal Concentration

A new alkaloid paenidigyamycin A (1) was obtained from the novel Ghanaian Paenibacillus sp. isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Ghana. Compound 1 was isolated on HPLC at tR = 37.0 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against L. major, 1 (IC50 0.75 µM) was just as effective as amphotericin B (IC50 0.31 µM). Against L. donovani, 1 (IC50 7.02 µM) was twenty-two times less active than amphotericin B (IC50 0.32 µM), reinforcing the unique effectiveness of 1 against L. major. For T. brucei brucei, 1 (IC50 0.78 µM) was ten times more active than the laboratory standard Coptis japonica (IC50 8.20 µM). The IC50 of 9.08 µM for 1 against P. falciparum 3d7 compared to artesunate (IC50 36 nM) was not strong, but this result suggests the possibility of using the paenidigyamycin scaffold for the development of potent antimalarial drugs. Against cercariae, 1 showed high anticercaricidal activity compared to artesunate. The minimal lethal concentration (MLC) and minimal effective concentration (MEC) of the compound were 25 and 6.25 µM, respectively, while artesunate was needed in higher quantities to produce such results. However, 1 (IC50 > 100 µM) was not active against T. mobilensis.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

scholarly journals Unusual derivatives from Hypericum scabrum

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sara Soroury ◽  
Mostafa Alilou ◽  
Thomas Gelbrich ◽  
Marzieh Tabefam ◽  
Ombeline Danton ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
2D Nmr ◽  
Moderate Activity ◽  
Trypanosoma Brucei Rhodesiense ◽  
L6 Cells ◽  
Aerial Parts ◽  
Hypericum Scabrum ◽  
New Compounds ◽  
Absolute Structure

AbstractThree new compounds (1–3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the first example of an esterified polycyclic polyprenylated acylphloroglucinol that features a unique tricyclo-[4.3.1.11,4]-undecane skeleton. Compound 2 is a fairly simple MPAP, but with an unexpected cycloheptane ring decorated with prenyl substituents, and compound 3 has an unusual 5,5-spiroketal lactone core. Their structures were determined by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, HRESI-TOFMS). Absolute configurations were established by ECD calculations, and the absolute structure of 2 was confirmed by a single crystal determination. Plausible biogenetic pathways of compounds 1–3 were also proposed. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and Plasmodium falciparum and cytotoxicity against rat myoblast (L6) cells were determined. Compound 1 showed a moderate activity against T. brucei and P. falciparum, with IC50 values of 3.07 and 2.25 μM, respectively.

scholarly journals In vitro life cycle of pentamidine-resistant amastigotes: stability of the chemoresistant phenotypes is dependent on the level of resistance induced.

1997 ◽  
Vol 41 (9) ◽  
pp. 1898-1903 ◽  
Author(s):  
D Sereno ◽  
J L Lemesre
Keyword(s):  
Life Cycle ◽  
Culture Conditions ◽  
Cross Resistance ◽  
Diminazene Aceturate ◽  
Drug Pressure ◽  
Mouse Macrophages ◽  
Wild Type Clone ◽  
Different Levels

Using a continuous drug pressure protocol, we induced pentamidine resistance in an active and dividing population of amastigote forms of Leishmania mexicana. We selected in vitro two clones with different levels of resistance to pentamidine, with clone LmPENT5 being resistant to 5 microM pentamidine, while clone LmPENT20 was resistant to 20 microM pentamidine. Resistance indexes (50% inhibitory concentration [IC50] after drug presure/IC50 before drug pressure) of 2 (LmPENT5) and 6 (LmPENT20) were determined after drug selection. Both resistant clones expressed significant cross-resistance to diminazene aceturate and primaquine. Pentamidine resistance was not reversed by verapamil, a calcium channel blocker known to reverse multidrug resistance (A. J. Bitonti, et al., Science 242:1301-1303, 1988; A. R. C. Safa et al., J. Biol. Chem. 262:7884-7888, 1987). No difference in the in vitro infectivity for resident mouse macrophages was observed between the wild-type clone (clone LmWT) and pentamidine-resistant clones. During in vitro infectivity experiments, when the life cycle was performed starting from the intramacrophagic amastigote stage, the drug resistance of the resulting LmPENT20 amastigotes was preserved even if the intermediate promastigote stage could not be considered resistant to 20 microM pentamidine. In the same way, when a complete developmental sequence of L. mexicana was achieved axenically by manipulation of appropriate culture conditions, the resulting axenically grown LmPENT20 amastigotes remained pentamidine resistant, whereas LmPENT5 amastigotes lost their ability to resist pentamidine, with IC50s and index of resistance values close to those for the LmWT clone. These results strongly indicate that the level of pentamidine tolerated by resistant amastigotes after the life cycle was dependent on the induced level of resistance. This fact could be significant in the in vivo transmission of drug-resistant parasites by Phlebotominae. Particular attention should be given to the finding that the emergence of parasite resistance is a potential risk of the use of inadequate doses as therapy in humans.

scholarly journals Histopathological Studies on the Effects of Chloroform and Methanolic Extracts of Ilex kudingcha in Trypanosoma brucei Infected Albino Wistar Rats

2018 ◽  
Vol 04 ◽  
pp. 50
Author(s):  
Olajoju. T. Soniran ◽  
Kalu. K. Ngele ◽  
Christopher. O. Alisa ◽  
Damilola. A. Omoboyowa ◽  
Nnabude. H. Agu ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Wistar Rats ◽  
Methanolic Extract ◽  
Phytochemical Analysis ◽  
Diminazene Aceturate ◽  
Leaf Extracts ◽  
Standard Drug ◽  
Phytochemical Study ◽  
Reference Drug ◽  
Histopathological Studies

Histopathological studies of the effects of chloroform and methanolic leaf extracts of Ilex kudingcha in Trypanosoma brucei infected albino wistar rats were investigated. The toxicity and phytochemical study were also carried out using standard protocol. T. brucei infected animals were administered orally with 200 and 400 mg/kg b.w. of the extracts and 3.5 mg/kg b.w. of the standard drug (diminazene aceturate). Results on acute toxicity studies (LD50) revealed no sign of lethality up to the dose of 5,000 mg/kg body weight but the liver and kidney histology of infected animals treated with 5,000 mg/kg b.w. of I. kudingcha extracts were observed to be hepatotoxic and nephrotoxic. The methanol extracts showed appreciably high in vivo anti-trypanosomal activities compared to the reference drug. Histological examination of the organs revealed serious pathological lesions in the liver of the infected animals without treatment (negative control). In the positive control animals (infected animals administered standard drug), mild multifocal aggregate of inflammatory leucocytes was observed. In the other experimental animals, no pathological lesion was observed in the liver, kidney, brain, and heart of infected animals treated with the methanolic extract and combined methanol and chloroform extracts. The effectiveness of the methanolic extract at reducing the lesions caused by the parasite is the same compared with the standard drug. Phytochemical analysis of the plant extracts showed that methanol extract contained appreciable high levels of alkaloids, saponin, tannins, phenol, and glycoside while flavonoid was not detected. Hence, the curative properties of methanolic extract of I. kudingcha as observed in the organs indicate its anti-trypanosomal properties but it should be consumed at minimal doses.

Cytotoxic constituents of Alocasia macrorrhiza

2017 ◽  
Vol 72 (1-2) ◽  
pp. 21-25 ◽  
Author(s):  
Marwa Elsbaey ◽  
Kadria F.M. Ahmed ◽  
Mahmoud F. Elsebai ◽  
Ahmed Zaghloul ◽  
Mohamed M.A. Amer ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Spectroscopic Data ◽  
Human Cancer ◽  
Indole Alkaloid ◽  
Acid Methyl Ester ◽  
2D Nmr ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Acid Methyl ◽  
First Time

AbstractAn indole alkaloid, 2-(5-hydroxy-1H-indol-3-yl)-2-oxo-acetic acid (1) isolated for the first time from nature, in addition to the nine known compounds 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (2), alocasin B (3), hyrtiosin B (4), α-monopalmitin (5), 1-O-β-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2(R)-hydroctadecanoyl) amido]-4,8-octadecadiene-1,3-diol (6), 3-epi-betulinic acid (7), 3-epi-ursolic acid (8),β-sitosterol (9) andβ-sitosterol 3-O-β-D-glucoside (10) were isolated from the rhizomes ofAlocasia macrorrhiza(Araceae). Their structures were elucidated by 1D and 2D NMR spectroscopic data. Of these compounds,6exhibited the strongest cytotoxicity against the four tested human cancer cell lines (IC50of about 10 µM against Hep-2 larynx cancer cells).

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