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In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

Kalani K, Kushwaha V, Sharma P, Verma R, Srivastava M, Khan F, Murthy PK, Srivastava SK - PLoS ONE (2014)

Bottom Line: The selectivity index (SI) of UA for the parasites was found safe.Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug.To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

View Article: PubMed Central - PubMed

Affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 (U.P.) India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, 110 001, India.

ABSTRACT
As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

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2D structure of Ursolic Acid (UA).
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pone-0111244-g002: 2D structure of Ursolic Acid (UA).

Mentions: ESI-MS m/z 457 [M+H]+, C30H48O3, 1H NMR (300 MHz, Pyridine): δ 0.77, 0.78, 0.98, 1.09, 1.14 (3H each, all s, 5 x tert. Me) 0.92 & 0.96 (3H each, each d, J = 6.4 and 7.3 Hz, 2 x sec Me), 2.82 (1H, d, J = 9.9 Hz, H-18 β), 3.20 (1H, dd, J = 6.8 & 8.7 Hz, H-3α). 13C NMR (75.5 MHz, Pyridine): C1- 39.5 (t), C2- 28.3 (t), C3- 78.7(d), C4- 39.9 (q), C5- 56.3 (d), C6- 19.1 (t), C 7- 33.9 (t), C8- 40.4 (q), C9- 47.0 (d), C10- 37.7 (q), C11- 23.9 (t), C12- 126.0 (d), C13- 139.6 (q), C14- 42.9 (q), C15- 28.9 (t), C16- 25.2 (t), C17- 48.5 (q), C18- 54.0 (d), C19- 30.5 (d), C20- 39.7 (d), C21- 31.3 (t), C22- 37.6 (t), C23- 29.0 (s), C24-15.8 (s), C25- 16.4 (s), C26- 17.5 (s), C27- 24.1 (s), C28- 179.7 (q), C29- 17.7 (s), C30- 21.4 (s) (Figure 2).


In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

Kalani K, Kushwaha V, Sharma P, Verma R, Srivastava M, Khan F, Murthy PK, Srivastava SK - PLoS ONE (2014)

2D structure of Ursolic Acid (UA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222910&req=5

pone-0111244-g002: 2D structure of Ursolic Acid (UA).
Mentions: ESI-MS m/z 457 [M+H]+, C30H48O3, 1H NMR (300 MHz, Pyridine): δ 0.77, 0.78, 0.98, 1.09, 1.14 (3H each, all s, 5 x tert. Me) 0.92 & 0.96 (3H each, each d, J = 6.4 and 7.3 Hz, 2 x sec Me), 2.82 (1H, d, J = 9.9 Hz, H-18 β), 3.20 (1H, dd, J = 6.8 & 8.7 Hz, H-3α). 13C NMR (75.5 MHz, Pyridine): C1- 39.5 (t), C2- 28.3 (t), C3- 78.7(d), C4- 39.9 (q), C5- 56.3 (d), C6- 19.1 (t), C 7- 33.9 (t), C8- 40.4 (q), C9- 47.0 (d), C10- 37.7 (q), C11- 23.9 (t), C12- 126.0 (d), C13- 139.6 (q), C14- 42.9 (q), C15- 28.9 (t), C16- 25.2 (t), C17- 48.5 (q), C18- 54.0 (d), C19- 30.5 (d), C20- 39.7 (d), C21- 31.3 (t), C22- 37.6 (t), C23- 29.0 (s), C24-15.8 (s), C25- 16.4 (s), C26- 17.5 (s), C27- 24.1 (s), C28- 179.7 (q), C29- 17.7 (s), C30- 21.4 (s) (Figure 2).

Bottom Line: The selectivity index (SI) of UA for the parasites was found safe.Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug.To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

View Article: PubMed Central - PubMed

Affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 (U.P.) India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, 110 001, India.

ABSTRACT
As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

Show MeSH
Related in: MedlinePlus