scholarly journals Synthesis and initial screening of lactate dehydrogenase inhibitor activity of 1,3-benzodioxole derivatives

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dicky Annas ◽  
Se-Yun Cheon ◽  
Mohammad Yusuf ◽  
Sung-Jin Bae ◽  
Ki-Tae Ha ◽  
...  

AbstractCancer is one of the main causes of mortality in the world. Many cancer cells produce ATP through high-level lactic acid fermentation catalyzed by lactate dehydrogenase (LDH), which converts pyruvic acid to lactic acid. LDH plays a dominant role in the Warburg effect, wherein aerobic glycolysis is favored over oxidative phosphorylation. Due to the high lactic acid production level in cancer cells, LDH-targeting could be a potential cancer treatment strategy. A few approaches, such as drug treatment, reportedly inhibited LDH activity. In this study, we describe new 1,3-benzodioxole derivatives that might be potential small molecule candidates for LDHA inhibition. The synthesis was carried out by trans-esterification between aryl ester and alcohol groups from piperonyl alcohol. Compounds 2 and 10 exhibited a selective LDHA IC50 value of 13.63 µM and 47.2 µM, respectively. Whereas only compound 10 showed significant cytotoxicity in several lines of cancer cells, especially in human pancreatic cancer PANC-1 cells. These synthesized compounds possess 2 aromatic rings and –CF3 moiety, which expectedly contributes to LDHA inhibition. The presented products have the potential to become a promising LDHA inhibitor drug candidate.

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 494 ◽  
Author(s):  
Kang Hyun Lee ◽  
Ye Won Jang ◽  
Jeongho Lee ◽  
Seunghee Kim ◽  
Chulhwan Park ◽  
...  

Biorefinery, which utilizes carbon-neutral biomass as a resource, is attracting attention as a significant alternative in a modern society confronted with climate change. In this study, spent coffee grounds (SCGs) were used as the feedstock for lactic acid fermentation. In order to improve sugar conversion, alkali pretreatment was optimized by a statistical method, namely response surface methodology (RSM). The optimum conditions for the alkali pretreatment of SCGs were determined as follows: 75 °C, 3% potassium hydroxide (KOH) and a time of 2.8 h. The optimum conditions for enzymatic hydrolysis of pretreated SCGs were determined as follows: enzyme complex loading of 30-unit cellulase, 15-unit cellobiase and 50-unit mannanase per g biomass and a reaction time of 96 h. SCG hydrolysates were used as the carbon source for Lactobacillus cultivation, and the conversions of lactic acid by L. brevis ATCC 8287 and L. parabuchneri ATCC 49374 were 40.1% and 55.8%, respectively. Finally, the maximum lactic acid production by L. parabuchneri ATCC 49374 was estimated to be 101.2 g based on 1000 g of SCGs through the optimization of alkali pretreatment and enzymatic hydrolysis.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Chae Hwan Hong ◽  
Si Hwan Kim ◽  
Ji-Yeon Seo ◽  
Do Suck Han

Polylactide (PLA), which is one of the most important biocompatible polyesters that are derived from annually renewable biomass such as corn and sugar beets, has attracted much attention for automotive parts application. The manufacturing method of PLA is the ring-opening polymerization of the dimeric cyclic ester of lactic acid, lactide. For the stereocomplex PLA, we developed the four unit processes, fermentation, separation, lactide conversion, and polymerization. Fermentation of sugars to D-lactic acid is little studied, and its microbial productivity is not well known. Therefore, we investigated D-lactic acid fermentation with a view to obtaining the strains capable of producing D-lactic acid, and we got a maximum lactic acid production 60 g/L. Lactide is prepared by a two-step process: first, the lactic acid is converted into oligo(lactic acid) by a polycondensation reaction; second, the oligo(lactic acid) is thermally depolymerized to form the cyclic lactide via an unzipping mechanism. Through catalyst screening test for polycondensation and depolymerization reactions, we got a new method which shortens the whole reaction time 50% the level of the conventional method. Poly(L-lactide) was obtained from the ring-opening polymerization of L-lactide. We investigated various catalysts and polymerization conditions. Finally, we got the best catalyst system and the scale-up technology.


REAKTOR ◽  
2017 ◽  
Vol 5 (2) ◽  
pp. 79
Author(s):  
Abdullah Abdullah ◽  
H. B. Mat

The liquid pineapple waste contain mainly sucrose, glucose, fructose, and other nutrients. It therefore can potentiall be used as carbon source for organic acid fermentation. Recently, lactic acid has been considered to be an important raw material for production of biodegradadable lactace polymer. The experiments weree carried out in shake flash fermentation using lactobacillus delbroeckii. Effect of some parameters such as temperature, initial Ph, initial substrate concentration, yeast extract concentration and fermentation time to the yield have been studied. The highest yield was 85.65% achieved at 40 0C, PH 6.00, 52.2 g/l sugar concentration with 5 g/l yeast extract. There was no significant increasing in lactic acid production was observed if supplementation of yeast extract above 10%.Keyword : lactic acid fermentation, liquid pineapple waste, lactobacillus delbrueckii


2019 ◽  
Vol 35 (1) ◽  
pp. 85-96
Author(s):  
Snezana Djordjevic ◽  
Violeta Mandic ◽  
Nikola Djordjevic ◽  
Biljana Pavlovic

Using of silage and haylage of forage legumes in ruminant nutrition and promotion of promoting proper forage conservation techniques should be an important strategy in livestock production in our country. Forage legumes are difficult to ensile, so it is necessary to apply the starter culture of selected strains of lactic acid bacteria that support the ensiling process and prevent bacterial butyric fermentation and thus contribute to the preservation and improvement of silage and haylage quality. In this paper, the influence of bacterial inoculant ?Silko for alfalfa? on the quality of silage and haylage of alfalfa in two separate trials is presented. The inoculant is a combination of homofermentative lactic bacteria Lactobacillus plantarum and Pediococcus spp. The first-cut alfalfa in the second year was used for silage and haylage. The silage was examined in mini-silos in the laboratory, and the haylage at the cattle farm where the plant material was cuts were collected in experimental silo bags. The treatments were control (untreated silage, i.e. haylage) and silage, i.e. haylage treated with inoculant ?Silko for alfalfa? (rate of 5 ml t-1 fresh material). The silages were analyzed after 90 days, and haylage after 40. The inoculant ?Silko for alfalfa? has been found to maintain the nutritive value of silage and haylage and to improve their chemical, energy and fermentation parameters relative to the control. Since ?Silko for alfalfa? positively affects the correct lactic acid fermentation of silage and haylage and contributes to a lesser loss of nutritional value and energy it is expected that it can promote a high level of productivity of ruminants, and thus contribute to the growth of profit in livestock production.


2020 ◽  
Vol 21 (5) ◽  
Author(s):  
WHINY HARDIYATI ERLIANA ◽  
Tri Widjaja ◽  
ALI ALTWAY ◽  
LILY PUDJIASTUTI

Abstract. Erliana WH, Widjaja T, Altway A, Pudjiastuti L. 2020. Synthesis of lactic acid from sugar palm trunk waste (Arenga pinnata): Hydrolysis and fermentation studies. Biodiversitas 21: 2281-2288. The increasing problems of global energy and the environment are the main reasons for developing products with new techniques through green methods. Sugar palm trunk waste (SPTW) has potential as agricultural waste because of its abundant availability, but it is not used optimally. This study was aimed to determine the effect of various microorganisms on increasing lactic acid production by controlling pH and temperature conditions in the fermentation process. SPTW contains 43.88% cellulose, 7.24% hemicellulose, and 33.24% lignin. The lignin content in SPTW can inhibit reducing sugar formation; the pretreatment process should remove this content. In the study, the pretreatment process was conducted using acid-organosolv. In the acid pretreatment, 0.2 M H2SO4 was added at 120oC for 40 minutes; organosolv pretreatment using 30% ethanol (v/v) at 107oC for 33 minutes was able to increase cellulose content by 56.33% and decrease lignin content by 27.09%. The pretreatment was followed by an enzymatic hydrolysis process with a combination of commercial cellulase enzymes from Aspergillus niger (AN) and Trichoderma reesei (TR), with variations of 0:1, 1:0, 1:1, 1:2 and 2:1. The best reducing sugar concentration was obtained with an AN: TR ratio of 1:2 to form reducing sugar from cellulose. Subsequently, lactic acid fermentation was carried out using lactic acid bacteria at 37oC and pH 6 incubated for 48 hours. The highest lactic acid concentration (33.292 g/L) was obtained using a mixed culture of Lactobacillus rhamnosus and Lactobacillus brevis to convert reducing sugar become lactic acid.


2009 ◽  
Vol 75 (15) ◽  
pp. 5175-5178 ◽  
Author(s):  
Kenji Okano ◽  
Shogo Yoshida ◽  
Tsutomu Tanaka ◽  
Chiaki Ogino ◽  
Hideki Fukuda ◽  
...  

ABSTRACT Optically pure d-lactic acid fermentation from arabinose was achieved by using the Lactobacillus plantarum NCIMB 8826 strain whose l-lactate dehydrogenase gene was deficient and whose phosphoketolase gene was substituted with a heterologous transketolase gene. After 27 h of fermentation, 38.6 g/liter of d-lactic acid was produced from 50 g/liter of arabinose.


Author(s):  
Micaela G. Chacón ◽  
Christopher Ibenegbu ◽  
David J. Leak

Abstract Objective A primary drawback to simultaneous saccharification and fermentation (SSF) processes is the incompatibility of the temperature and pH optima for the hydrolysis and fermentation steps—with the former working best at 50–55 °C and pH 4.5–5.5. Here, nine thermophilic Bacillus and Parageobacillus spp. were evaluated for growth and lactic acid fermentation at high temperature and low pH. The most promising candidate was then carried forward to demonstrate SSF using the cellulosic fraction from municipal solid waste (MSW) as a feedstock. Results B. smithii SA8Eth was identified as the most promising candidate and in a batch SSF maintained at 55 °C and pH 5.0, using a cellulase dose of 5 FPU/g glucan, it produced 5.1 g/L lactic acid from 2% (w/v) MSW cellulosic pulp in TSB media. Conclusion This work has both scientific and industrial relevance, as it evaluates a number of previously untrialled bacterial hosts for their compatibility with lignocellulosic SSF for lactic acid production and successfully identifies B. smithii as a potential candidate for such a process.


2006 ◽  
Vol 72 (8) ◽  
pp. 5492-5499 ◽  
Author(s):  
Minoska Valli ◽  
Michael Sauer ◽  
Paola Branduardi ◽  
Nicole Borth ◽  
Danilo Porro ◽  
...  

ABSTRACT Yeast strains expressing heterologous l-lactate dehydrogenases can produce lactic acid. Although these microorganisms are tolerant of acidic environments, it is known that at low pH, lactic acid exerts a high level of stress on the cells. In the present study we analyzed intracellular pH (pHi) and viability by staining with cSNARF-4F and ethidium bromide, respectively, of two lactic-acid-producing strains of Saccharomyces cerevisiae, CEN.PK m850 and CEN.PK RWB876. The results showed that the strain producing more lactic acid, CEN.PK m850, has a higher pHi. During batch culture, we observed in both strains a reduction of the mean pHi and the appearance of a subpopulation of cells with low pHi. Simultaneous analysis of pHi and viability proved that the cells with low pHi were dead. Based on the observation that the better lactic-acid-producing strain had a higher pHi and that the cells with low pHi were dead, we hypothesized that we might find better lactic acid producers by screening for cells within the highest pHi range. The screening was performed on UV-mutagenized populations through three consecutive rounds of cell sorting in which only the viable cells within the highest pHi range were selected. The results showed that lactic acid production was significantly improved in the majority of the mutants obtained compared to the parental strains. The best lactic-acid-producing strain was identified within the screening of CEN.PK m850 mutants.


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