Synthesis and activity of BNF15 against drug-resistant Mycobacterium tuberculosis

Author(s):  
Hafij Al Mahmud ◽  
Hoonhee Seo ◽  
Sukyung Kim ◽  
Md Imtiazul Islam ◽  
Omme Fatema Sultana ◽  
...  

Aim: Tuberculosis is the leading cause of mortality among infectious diseases worldwide. Finding a new competent anti tubercular therapy is essential. Materials & methods: We screened thousands of compounds and evaluated their efficacy against Mycobacterium tuberculosis. Results: Initially, 2-nitronaphtho[2,3-b]benzofuran-6,11-dione was active against M. tuberculosis. Next, among x15 newly synthesized derivatives, BNF15 showed promising effect against all drug-sensitive and drug-resistant M. tuberculosis (MIC: 0.02–0.78 μg/ml). BNF15 effectively killed intracellular M. tuberculosis and nontuberculous mycobacteria. BNF15 exhibited a prolonged post antibiotic effect superior to isoniazid, streptomycin, and ethambutol and synergistic interaction with rifampicin. In acute oral toxicity test, BNF15 did not show toxic effect at a concentration up to 2000 mg/kg. Conclusion: These results highlight the perspective of BNF15 to treat drug-resistant M. tuberculosis.

2020 ◽  
Author(s):  
Henna Sood ◽  
Yashwant Kumar ◽  
Vipan Kumar Gupta ◽  
Daljit Singh Arora

Abstract Background: The increased occurrence of the antibiotic resistance has added up to the misery of mankind. There is an immediate need to search alternatives and Symplocos racemosa is one such potent medicinal plant . The aim of the study was to explore various activities of its phytoconstituents, confirm their biosafety and identify the active components.Methods: The ethylacetate extract and the major group of phytoconstituents were tested for minimal inhibitory concentration, viable cell count studies, Post antibiotic effect, activity against 34 multi-drug resistant microorganisms, anti-biofilm and anti proliferative potential. The biosafety was evaluated by Ames and MTT assay. In vivo safety of flavonoids was determined by acute oral toxicity test using Swiss albino mice. The antimicrobial components in flavonoids were also identified by using TLC and GC-MS analysis.Results: Ethyl acetate was the best organic extractant. The phytochemical analyses revealed the presence of flavonoids, cardiac glycosides, saponins, tannins, triterpenes and Phytosterols. Flavonoids exhibited the highest antimicrobial potential whereas tannins, triterpenes and phytosterols were completely inactive. Their Minimum Inhibitory Concentration ranged from 0.5-10 mg/ml; exhibited a bactericidal mode of action and a prolonged post antibiotic effect. The phytoconstituents displayed a significant antibiofilm potential by inhibiting the initial cell attachment, disrupting the pre-formed biofilms and reducing the metabolic activity of biofilms. The phytoconstituents were significantly active against the drug-resistant strains of E.coli , MRSA and Salmonella spp. Flavonoids showed significant cytotoxic effect against the RD, L20B and Hep2 cell lines (IC 50 361-494 µg/ml). All the test extracts were biosafe as depicted by the Ames test, MTT assay. Also, flavonoids did not induce any abnormality in biochemical parameters and Organs’ histopathology of the Swiss albino mice during the in vivo acute oral toxicity studies. The flavonoids were resolve into 4 bands (S1-S4) using TLC, where S3 was the most active and its GC-MS analysis revealed the presence of Bicyclo [2.2.1]heptan-2-one,1,7,7-trimethyl-, (1S)- at an RT of 11.14 as the major compound.Conclusions: These findings suggest that Symplocos racemosa bark could be a potential source of antimicrobial metabolites, which could substantially contribute to the arsenal of existing natural drugs for combating the antimicrobial resistance.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Florence Nalimu ◽  
Joseph Oloro ◽  
Emanuel L. Peter ◽  
Patrick Engeu Ogwang

Abstract Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.


Author(s):  
Poojita K ◽  
Fajeelath Fathima ◽  
Rajdeep Ray ◽  
Lalit Kumar ◽  
Ruchi Verma

Tuberculosis is one of the leading cause of increase in mortality rate in today’s health care scenario. Due to increase frequency of drug resistant TB it is prudent to find new targets and promising targets for anti-tubercular activity. MmpL3 (Mycobacterial Membrane Protein Large 3) is one of the most effective and promiscuous targets for development of new drug for anti-tubercular therapy due to its cross resistance inhibition property. In this study we have presented atom based 3D QSAR and finger print based 2D QSAR models to study different structural and functional groups of Adamantyl urea derivatives and their action in MmpL3 inhibitory activity which will provide us the insight for designing better and far more effective anti TB drugs.


Author(s):  
PANDU SALIM HANAFI ◽  
AJI SUTRISNO ◽  
TUTIK MURNIASIH ◽  
HARIJONO ◽  
MASTERIA YUNOVILSA PUTRA ◽  
...  

Objective: This study aimed to evaluate the toxicological potential of the ethanol extract of Holothuria atra through the acute oral toxicity – acute toxic class method. Methods: The sample was immersed in ethanol for 72 h at room temperature and repeated 3 times. The extracts were evaporated using a vacuum rotary evaporator. The identification of compounds in the ethanol extract of H. atra was carried out using liquid chromatography–mass spectrometry (LCMS) analysis. The acute toxicity test was examined the effects of treating male mice with the ethanol extract of H. atra at 300 and 2000 mg/kg by oral administration for 14 days. On the past day of the toxicity test, liver of all experimental animals was taken for histopathological testing. Results: LCMS analysis showed that the ethanol extract of H. atra is contained polar compounds (chlorogenic acid, coumaric acid, a glycosaminoglycan, and holothurin) and non-polar compounds (fatty acids). Acute toxicity study was performed at a dose of 300 and 2000 mg/kg for 14 consecutive days. No deaths or behavioral changes were observed during the administration of both doses. Histopathological test results on the liver showed a few changes at doses of 2000 mg/kg. Conclusions: The LD50 is equal to 5000 mg/kg and the ethanol extracts of H. atra can be classified as practically nontoxic. However, further studies are required to proceed to clinical studies in humans.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Henna Sood ◽  
Yashwant Kumar ◽  
Vipan Kumar Gupta ◽  
Daljit Singh Arora

Abstract Background Plants provide a ray of hope to combat the ever increasing antibiotic resistance and Symplocos racemosa is a valuable medicinal plant. The study focused on highlighting the importance of this plant’s phytoconstituents as potential source of novel antimicrobials against planktonic as well as biofilm forming microorganisms, along with their antiproliferative activity. The biosafety of the phytoconstituents was also established, followed by detection of probable antimicrobial components. Methods The best organic extractant and major groups of phytoconstituents were tested for their antimicrobial activity against reference microbial strains and drug-resistant clinical isolates. The anti-proliferative potential of the most active group of phytoconstituents was evaluated against cancerous cell lines. The in vitro biosafety of phytoconstituents was evaluated by Ames and MTT assay, while in vivo biosafety of the most active phytoconstituents, i.e., flavonoids was determined by acute oral toxicity. Further, the probable antimicrobial components in the flavonoids were detected by TLC and GC-MS. Results Ethyl acetate extract was the most effective among various organic extracts, whereas phytoconstituents such as flavonoids, cardiac glycosides, saponins, tannins, triterpenes and phytosterols were the major groups present, with flavonoids being the most potent antimicrobials. The phytoconstituents displayed a significant antibiofilm potential, as exhibited by inhibition of initial cell attachment, disruption of the pre-formed biofilms and reduced metabolic activity of biofilms. The phytoconstituents were significantly active against the drug-resistant strains of E.coli, MRSA and Salmonella spp. Further, flavonoids showed significant cytotoxic effect against the cancerous cell lines but were non-cytotoxic against Vero (normal) cell line. All the test preparations were biosafe, as depicted by the Ames test and MTT assay. Also, flavonoids did not induce any abnormality in body weight, clinical signs, biochemical parameters and organs’ histopathology of the Swiss albino mice during in vivo acute oral toxicity studies. The flavonoids were resolved into 4 bands (S1-S4), where S3 was the most active and its GC-MS analysis revealed the presence of a number of compounds, where Bicyclo [2.2.1]heptan-2-one,1,7,7-trimethyl-, (1S)- was the most abundant. Conclusions These findings suggest that the phytoconstituents from Symplocos racemosa bark could act as potential source of antimicrobial as well as antiproliferative metabolites.


Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1144
Author(s):  
Yang Li ◽  
Baozhu Guo ◽  
Chong Li ◽  
Weiwei Wang ◽  
Zhengke Wu ◽  
...  

The aims of this study were to screen and isolate a highly efficient strain from the rumen of a cow that can degrade the antigenic soy proteins in soybean meal (SBM) and improve the nutritional value of SBM by fermenting it with this strain. The safety of this strain was investigated with an acute oral toxicity test. A Bacillus amyloliquefaciens strain was successfully screened with plate tests and fermentation. After solid state fermentation of SBM with B. amyloliquefaciens for 24 h, the amounts of glycinin and β-conglycinin, two major antigenic proteins in SBM, decreased by 92.32% and 85.05%, respectively. The crude protein content in the fermented soybean meal (FSBM) increased by 17.54% compared with that in SBM. Notably, the trichloroacetic-acid-soluble protein (TCA-SP) content, particularly small peptides and free amino acids, was 9.97-fold higher in FSBM than in SBM. The in vitro dry matter digestibility and digestible energy of SBM increased from 62.91% to 72.52% and from 10.42 MJ/kg to 13.37 MJ/kg (dry matter basis), respectively, after fermentation. The acute oral toxicity test suggested that the strain exerted no harmful effects on the relative organ weights, the morphological tissue structure, or the health of mice. These results indicate that the B. amyloliquefaciens strain isolated in this study is a safe strain for animals, and could be used to improve the nutritional quality of SBM by solid-state fermentation.


Author(s):  
F.O Awobajo ◽  
E Omorodion-Osagie ◽  
I.I Olatunji-Bello ◽  
O.A Adegoke ◽  
T.L Adeleke

2018 ◽  
Vol 33 (3) ◽  
pp. 214-219
Author(s):  
Chang-Woo Lim ◽  
◽  
Song Ee Son ◽  
Hu Jang Lee

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