Omics-Driven Knowledge-Based Discovery of Anthelmintic Targets and Drugs

Tyagi, Rahul; Rosa, Bruce A.; Mitreva, Makedonka

doi:10.1016/b978-0-12-816125-8.00012-2

Cited by 3 publications

(3 citation statements)

References 148 publications

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“…Regarding fatty acids, such as those identified in G. sepium , a few studies have evaluated their anthelmintic effects; some have shown that these fatty acids probably have the ability to act either individually or together. With respect to azelaic acid specifically, identified its possible effect on Caenorhabditis elegans [ 82 ], which was suggested to be associated with the activity of the steroid enzyme 5 alpha-reductase [ 83 ]. Other authors have reported AA against nematodes such as Meloidogyne incognita [ 84 ], Oesophagostomum dentatum [ 85 ], Haemonchus spp., Oesophagostomum spp., and Trichostrongylus [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Anthelmintic Evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint Analysis of Extracts by UHPLC-Orbitrap Mass Spectrometry

et al. 2020

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In the present work, the anthelmintic activity (AA) of ethanolic extracts obtained from Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce was evaluated using the third-stage-larval (L3) exsheathment inhibition test (LEIT) and egg hatch test (EHT) on Haemonchus contortus. Extracts were tested at concentrations of 0.3, 0.6, 1.2, 2.5, 5.0, 10, 20, and 40 mg/mL. The larval exsheathment inhibition (LEI) results showed that G. sepium achieved the highest average inhibition of 91.2%, compared with 44.6% for P. dulce and 41.0% for L. leucocephala at a concentration of 40 mg/mL; the corresponding IC50 values were 22.4, 41.7, and 43.3 mg/mL, respectively. The rates of egg hatching inhibition (EHI) at a concentration of 5 mg/mL were 99.5% for G. sepium, 64.2% for P. dulce, and 54% for L. leucocephala; the corresponding IC50 values were 1.9 mg/mL for G. sepium, 3.9 mg/mL for P. dulce, and 4.3 mg/mL for L. leucocephala. The species extracts studied here were also analyzed by ultra-high performance liquid chromatography and Orbitrap high resolution mass spectrometry (UHPLC-Q/Orbitrap/MS/MS), resulting in the compounds’ identification associated with AA. Glycosylated flavonoids and methoxyphenols were observed in all three species: fatty acids in G. sepium and P. dulce; phenylpropanoids, anthraquinone glycosides, amino acids and glycosylated phenolic acids in G. sepium; and flavonoids in L. leucocephala. Comparatively, G. sepium presented a greater diversity of compounds potentially active against the control of gastrointestinal nematodes, which was associated with the results obtained in the applied tests.

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Section: Discussionmentioning

confidence: 99%

In Vitro Anthelmintic Evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint Analysis of Extracts by UHPLC-Orbitrap Mass Spectrometry

et al. 2020

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“…< 500 Da), H-bond donors (HBDs: < 5), H-bond acceptors (HBAs: < 10), rotatable bonds (< 10), topological polar surface area (TPSA) not exceeding the thresholds of 140 Å 2 and octanolwater partition coefficient (Log P) not exceeding the value of 5. [11] The initial drug-likeness analysis showed that all the newly synthesized spirooxindole-oxofurans(4 a-d)fell within the acceptable scores of Lipinski's rules of five, and Veber's violations were not found (Table 3). Briefly, the MW of all the synthesized spirooxindole-oxofuran was less than 500 Daltons, whereas the number of HBDs and HBAs for4 a-d was recorded at the desirable thresholds of less than 5 and 10, respectively.…”

Section: Computational Chemistryspirooxindole-oxofurans (4 A-d) Exert...mentioning

confidence: 95%

Synthesis of Functionalized 2′,5‐Oxo‐spiro[furan‐2,3′‐indoline]‐3‐carboxylate Derivatives as Antiproliferative Agents: ADMET Studies, and Molecular Docking against P2Y12 Inhibitors

et al. 2023

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Herein, we present a one‐pot, three‐component synthesis of spirooxindole‐oxofuran carboxylate derivatives (4 a–d) through the Huisgen reaction. The newly synthesized spirocyclic compounds were tested for in vitroantiproliferative efficacy against 60 human cancer cell lines at the National Cancer Institute (NCI) in the United States. The screening results indicated that two spirooxindole compounds, 4 b and4 c, possessed the strongest anti‐cancer efficacy in terms of percentage growth inhibition (% GI), with values of 34.17 and 38.19 at 10−5 M concentration against the CNS cancer panel‘s SNB‐75 cell line, respectively. Furthermore, molecular docking investigations demonstrated the binding affinity for the P2Y12 receptor. The compound 4 c which exhibited strong antiproliferative activity with high binding energies might therefore, serve as a potential lead molecule for the development of more effective anti‐cancer agents.

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“…Lipinski et al analyzed the properties of such molecules and formulated a set of rules that describe the molecules highly likely to be able to pass through the BBB [78]. The so-called Lipinski's rule says that the therapeutic molecule is more likely to demonstrate a higher adsorption or permeation if it has less than 5 H-bonds, less than 10 H-acceptors and calculated Log P less than 5, and its molecular weight is no greater than 500 [79]. Development and testing of novel therapeutic molecules is an extremely long and expensive process, and Lipinski's rule helps to accelerate it [80].…”

Section: Lipinski's Rulementioning

confidence: 99%

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

et al. 2022

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Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood–brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors. Graphical Abstract

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Omics-Driven Knowledge-Based Discovery of Anthelmintic Targets and Drugs

Cited by 3 publications

References 148 publications

In Vitro Anthelmintic Evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint Analysis of Extracts by UHPLC-Orbitrap Mass Spectrometry

In Vitro Anthelmintic Evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint Analysis of Extracts by UHPLC-Orbitrap Mass Spectrometry

Synthesis of Functionalized 2′,5‐Oxo‐spiro[furan‐2,3′‐indoline]‐3‐carboxylate Derivatives as Antiproliferative Agents: ADMET Studies, and Molecular Docking against P2Y12 Inhibitors

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

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