scholarly journals In vitro Screening of Antileishmanial Activity of Natural Product Compounds: Determination of IC50, CC50 and SI Values

BIO-PROTOCOL ◽  
2019 ◽  
Vol 9 (21) ◽  
Author(s):  
Olga Koutsoni ◽  
Kalliopi Karampetsou ◽  
Eleni Dotsika
Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2630 ◽  
Author(s):  
Pankaj Pandey ◽  
Kuldeep Roy ◽  
Haining Liu ◽  
Guoyi Ma ◽  
Sara Pettaway ◽  
...  

Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects. We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics. In search of new chemotypes as CB1 antagonists, we screened the in silico purchasable natural products subset of the ZINC12 database against our reported CB1 receptor model using the structure-based virtual screening (SBVS) approach. A total of 18 out of 192 top-scoring virtual hits, selected based on structural diversity and key protein–ligand interactions, were purchased and subjected to in vitro screening in competitive radioligand binding assays. The in vitro screening yielded seven compounds exhibiting >50% displacement at 10 μM concentration, and further binding affinity (Ki and IC50) and functional data revealed compound 16 as a potent and selective CB1 inverse agonist (Ki = 121 nM and EC50 = 128 nM) while three other compounds—2, 12, and 18—were potent but nonselective CB1 ligands with low micromolar binding affinity (Ki). In order to explore the structure–activity relationship for compound 16, we further purchased compounds with >80% similarity to compound 16, screened them for CB1 and CB2 activities, and found two potent compounds with sub-micromolar activities. Most importantly, these bioactive compounds represent structurally new natural product chemotypes in the area of cannabinoid research and could be considered for further structural optimization as CB1 ligands.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yongchang Li ◽  
Mohamed Abdo Rizk ◽  
Eloiza May Galon ◽  
Mingming Liu ◽  
Jixu Li ◽  
...  

In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selected compounds were evaluated using B. microti “rodent strain” in mice model. Three potent compounds, namely, Rottlerin (RL), Narasin (NR), Lasalocid acid (LA), exhibited the lowest IC50 (half-maximal inhibitory concentration) as follows: 5.45 ± 1.20 μM for RL, 1.86 ± 0.66 μM for NR, and 3.56 ± 1.41 μM for LA. The viability result revealed the ability of RL and LA to prevent the regrowth of treated parasite at 4 × IC50 and 2 × IC50, respectively, while 4 × IC50 of NR was sufficient to stop the regrowth of parasite. The hematology parameters of B. microti in vivo were different in the NR-treated groups as compared to the infected/untreated group. Interestingly, intraperitoneal administration of NR exhibiting inhibition in the growth of B. microti in mice was similar to that observed after administration of the commonly used antibabesial drug, diminazene aceturate (DA) (76.57% for DA, 74.73% for NR). Our findings indicate the richness of natural product compounds by novel potent antibabesial candidates, and the identified potent compounds, especially NR, might be used for the treatment of animal babesiosis.


Agronomy ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 598
Author(s):  
César A. Hernández-Pérez ◽  
Fernando Carlos Gómez-Merino ◽  
José L. Spinoso-Castillo ◽  
Jericó J. Bello-Bello

Water stress caused by drought affects the productivity of the sugarcane crop. A breeding alternative is the selection of drought-tolerant sugarcane cultivars. The objective of this study was the in vitro screening of cultivars tolerant to water stress using polyethylene glycol (PEG) as a stressing agent. Cultivars (cv) Mex 69-290, CP 72-2086, Mex 79-431 and MOTZMex 92-207 were subjected to different concentrations of PEG 6000 (0, 3, 6 and 9% w/v) using Murashige and Skoog semi-solid culture medium. At 30 days of culture, different developmental variables and dry matter (DM), total protein (TP), proline (Pr) and glycine-betaine (GB) contents were evaluated. The results showed reduced development in cv CP 72-2086, Mex 79-431 and MOTZMex 92-207 with increasing PEG concentration. The cv Mex 69-290 showed tolerance to osmotic stress of −0.45 MPa using 3% PEG. Overall, TP content decreased with increasing PEG concentration, while DM, Pr and GB contents rose with increasing PEG concentration in all evaluated cultivars. Our results suggest that cv Mex 69-290 has a slight tolerance to water stress and could be used for rainfed cultivation with low rainfall or reduced irrigation for better water use efficiency. In conclusion, the in vitro screening technique of cultivars tolerant to PEG-induced water stress is an alternative for early determination of drought stress in sugarcane.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
W Jülich ◽  
J Pörksen ◽  
H Welzel ◽  
U Lindequist
Keyword(s):  

Planta Medica ◽  
2013 ◽  
Vol 79 (13) ◽  
Author(s):  
GN Ndlovu ◽  
G Fouche ◽  
W Cordier ◽  
V Steenkamp ◽  
M Tselanyane

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 405-416 ◽  
Author(s):  
M. R Hardeman ◽  
Carina J L. Heynens

SummaryStorage experiments were performed at 4°, 25° and 37° C with platelet-rich plasma under sterile conditions. In some experiments also the effect of storing platelets at 4° C in whole blood was investigated.Before, during and after three days of storage, the platelets were tested at 37° C for their serotonin uptake and response to hypotonic shock. In addition some glycolytic intermediates were determined.A fair correlation was noticed between the serotonin uptake and hypotonic shock experiments. Both parameters were best maintained at 25° C. Also platelet counting, performed after the storage period, indicated 25° C as the best storage temperature. Determination of glycolytic intermediates did not justify any conclusion regarding the optimal storage temperature. Of the various anticoagulants studied, ACD and heparin gave the best results as to the serotonin uptake and hypotonic shock response, either with fresh or stored platelets. The use of EDTA resulted in the lowest activity, especially after storage.The results of these storage experiments in vitro, correspond well with those in vivo reported in the literature.


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