106757-10-2Relevant academic research and scientific papers
Synthesis and anticancer activity of hybrid molecules based on lithocholic and (5Z,9Z)-tetradeca-5,9-dienedioic acids linked via mono(di,tri,tetra)ethylene glycol and α,ω-diaminoalkane units
D’yakonov, Vladimir A.,Tuktarova, Regina A.,Dzhemileva, Lilya U.,Ishmukhametova, Svetlana R.,Dzhemilev, Usein M.
, p. 1 - 29 (2021)
For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)- 1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2-4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.
Synthesis of spiroannulated oligopyrrole macrocycles derived from lithocholic acid
Huong, Nguyen Thi Thu,Klimkova, Petra,Sorrenti, Alessandro,Mancini, Giovanna,Drasar, Pavel
, p. 715 - 720 (2009)
Two new steroidal spiroannulated calix[4]pyrroles 5 and 10, derived from bile acids (lithocholate), were prepared by the acid catalyzed condensation of methyl-3,3-bis(pyrrol-2-yl)-5β-cholan-24-oate 3 with carbonyl compounds and with 2,2′-propane-2,2-diylbis(1H-pyrrole), respectively. The new compounds were fully characterized by physicochemical methods.
SYNTHESE D'ANTIBIOTIQUES TRITERPENIQUES A PARTIR D'ACIDES BILIAIRES. IV . ETUDE DE L'HYDROGENATION CATALYTIQUE DU DIMETHYL-4,4 CHOLENE-5 ONE-3 OATE-24 DE METHYLE.
Aranda, G.,Fetizon, M.,Tayeb, N.
, p. 4147 - 4158 (1987)
Catalytic hydrogenation of methyl 4,4 dimethyl chol-5 en-3-one-24 oate, prepared from lithocholic acid has been carefully studied in a variety of conditions (solvent, temperature, pressure, nature and amount of catalyst) .Fairly mild conditions have been found, which lead to the 5α dihydroderivative, and do not affect the Δ8(9) double bond of lanosterol.Therefore, one of the major difficulties of the conversion of bile acids into tetracyclic triterpene antibiotics has been overcome .
Deciphering the role of charge, hydration, and hydrophobicity for cytotoxic activities and membrane interactions of bile acid based facial amphiphiles
Singh, Manish,Singh, Ashima,Kundu, Somanath,Bansal, Sandhya,Bajaj, Avinash
, p. 1926 - 1937 (2013)
We synthesized four cationic bile acid based facial amphiphiles featuring trimethyl ammonium head groups. We evaluated the role of these amphiphiles for cytotoxic activities against colon cancer cells and their membrane interactions by varying charge, hydration and hydrophobicity. The singly charged cationic Lithocholic acid based amphiphile (LCA-TMA1) is most cytotoxic, whereas the triply charged cationic Cholic acid based amphiphile (CA-TMA 3) is least cytotoxic. Light microscopy and Annexin-FITC assay revealed that these facial amphiphiles caused late apoptosis. In addition, we studied the interactions of these amphiphiles with model membrane systems by Prodan-based hydration, DPH-based anisotropy, and differential scanning calorimetry. LCA-TMA1 is most hydrophobic with a hard charge causing efficient dehydration and maximum perturbations of membranes thereby facilitating translocation and high cytotoxicity against colon cancer cells. In contrast, the highly hydrated and multiple charged CA-TMA3 caused least membrane perturbations leading to low translocation and less cytotoxicity. As expected, Chenodeoxycholic acid and Deoxycholic acid based amphiphiles (CDCA-TMA2, DCA-TMA2) featuring two charged head groups showed intermediate behavior. Thus, we deciphered that charge, hydration, and hydrophobicity of these amphiphiles govern membrane interactions, translocation, and resulting cytoxicity against colon cancer cells.
Counteracting in Vitro Toxicity of the Ionophoric Mycotoxin Beauvericin - Synthetic Receptors to the Rescue
Ornelis, Vincent,Rajkovic, Andreja,Decleer, Marlies,Sas, Benedikt,De Saeger, Sarah,Madder, Annemieke
, p. 10422 - 10435 (2019)
Beauvericin (BEA) and enniatins are toxic ionophoric cyclodepsipeptides that mainly occur in grains. As such, their presence in food commodities poses a concern for public health. To date, despite recent European Food Safety Authority emphasis on the need for more data to evaluate long-term toxicity effects, no suitable affinity reagents are available to detect the presence of BEA and derivatives in food samples. We here report on the synthesis of a small library of artificial receptors with varying cavity sizes and different hydrophobic building blocks. Immobilization of one of the receptors on solid support resulted in a strong retention of beauvericin, thus revealing promising properties as solid-phase extraction material for sample pretreatment. Furthermore, treatment of HepG2 cells with the most promising receptor markedly reduced beauvericin-induced cytotoxicity, hinting toward the possibility of using synthetic receptors as antidotes against ionophoric toxins.
Bile acid amphiphiles with tunable head groups as highly selective antitubercular agents
Bansal, Sandhya,Singh, Manish,Kidwai, Saqib,Bhargava, Priyanshu,Singh, Ashima,Sreekanth, Vedagopuram,Singh, Ramandeep,Bajaj, Avinash
, p. 1761 - 1768 (2014)
Tuberculosis faces major challenges for its cure due to (a) long treatment period, (b) emergence of drug resistance bacteria, and (c) poor patient compliance. Disrupting the membrane integrity of mycobacteria as a therapeutic strategy has not been explored well as the rigid, waxy, and hydrophobic nature of mycobacterial lipids does not allow binding and penetration of charged amtimicrobial amphiphiles and peptides. Here, we present a new concept that fine-tuning of the charged head group modulates the specificity of amphiphiles against bacterial membranes. We show that hard-charged amphiphiles interact with mycobacterial trehalose dimycolates and penetrate through rigid mycobacterial membranes. In contrast, soft-charged amphiphiles specifically inhibit the growth of both E. coli and S. aureus via electrostatic interactions. These subtle variations between interactions of amphiphiles and bacterial membranes could be explored further to design more specific and potent antimycobacterial agents. This journal is
Synthesis of novel dimeric compounds containing triazole using click method and their selective antiproliferative and proapoptotic potential via mitochondrial apoptosis signaling
Karabulut, H. R. Ferhat,Karatavuk, Ali Osman,Ozyildirim, Hasan,Do?anlar, O?uzhan,Do?anlar, Zeynep Banu
, p. 643 - 655 (2020)
In this study, the main aim was synthesis of dimeric compounds, which contain lithocholic acid and a triazole structure to investigate the selective cellular and molecular antiproliferative and proapoptotic potential of these products in healthy embryonic fibroblast (MEF), cervix cancer (HeLa), and breast cancer (MCF-7) cells. Four ester (5a–d) and five dimeric (6a–d, 7) out of nine novel compounds were obtained. First of all, lithocholic acid was converted to methyl lithocholate and then it was reacted with certain alkynoic acids (a–d) to obtain its alkynoate derivatives (5a–d). Finally, these compounds were converted to dimers (6a–d) by using 2,6-bis(azidomethyl)pyridine via the click method. Our result indicate that, treatment with dimeric compounds can selectively decrease the cell viability and proliferation in cervix cancer HeLa and breast cancer MCF-7 cells, except 7 which caused a strong cytotoxicity on healthy MEF cells. According to MTT assay, Nucblue cell stain and Annexin V/Propodium iodide molecular probe staining, 100 μM concentrations of the dimeric compounds was sufficient in inducing death and apoptotic cell ratio in HeLa and MCF-7 breast cancer cells selectively. In brief, the present study indicates that most effective dimeric compounds are 6a and 6b, which have the highest IC50 (345.8–342.6 μM) value on healthy cell and the lowest IC50 value in both cervix (49.2–36.9 μM) and breast (23.0–66.1 μM) cancer cells especially long-term treatment and which triggers apoptosis pathway specifically.
Development of novel lithocholic acid derivatives as vitamin D receptor agonists
Masuno, Hiroyuki,Kazui, Yuko,Tanatani, Aya,Fujii, Shinya,Kawachi, Emiko,Ikura, Teikichi,Ito, Nobutoshi,Yamamoto, Keiko,Kagechika, Hiroyuki
, p. 3674 - 3681 (2019)
Lithocholic acid (2) was identified as the second endogenous ligand of vitamin D receptor (VDR), though its binding affinity to VDR and its vitamin D activity are very weak compared to those of the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1). 3-Acylated lithocholic acids were reported to be slightly more potent than lithocholic acid (2) as VDR agonists. Here, aiming to develop more potent lithocholic acid derivatives, we synthesized several derivatives bearing a 3-sulfonate/carbonate or 3-amino/amide substituent, and examined their differentiation-inducing activity toward human promyelocytic leukemia HL-60 cells. Introduction of a nitrogen atom at the 3-position of lithocholic acid (2) decreased the activity, but compound 6 bearing a 3-methylsulfonate group showed more potent activity than lithocholic acid (2) or its acylated derivatives. The binding of 6 to VDR was confirmed by competitive binding assay and X-ray crystallographic analysis of the complex of VDR ligand-binding domain (LBD) with 6.
Transamination reactions with multiple turnovers catalyzed by hydrophobic pyridoxamine cofactors in the presence of polyethylenimine polymers
Liu, Lei,Zhou, Wenjun,Chruma, Jason,Breslow, Ronald
, p. 8136 - 8137 (2004)
Pyridoxamines carrying hydrophobic side chains reversibly bind into the hydrophobic core of polyethylenimines and transaminate ketoacids to amino acids with as much as a 725000-fold rate acceleration. Turnover catalysis was achieved by sacrificial oxidative decarboxylation of C-substituted amino acids, which reconverted the pyridoxals to pyridoxamines. Copyright
Synthesis and characterization of novel bile-acid - heteroaryl conjugates with N-(2-aminoethyl)amido linker
Koivukorpi, Juha,Valkonen, Arto,Lahtinen, Manu,Kolehmainen, Erkki
, p. 53 - 57 (2008)
Four novel bile acid conjugates N-[2-([2,2′]-bithiophen-5-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (1), N-[2-([2,2′]-bithiophen-5-ylmethyl)aminoethyl]-3α,7α,12α-trihydroxy-5β-cholan-24-amide (2), N-[2-(1H-pyrrol-2-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (3), N-[2-(pyridin-2-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (4) have been synthesized in moderate to good yields, and their structures have been characterized by 1H, 13C, 13C DEPT-135, PFG 1H,13C HMQC, and PFG 1H,13C HMBC NMR spectra. Their molecular weights and elemental compositions have been determined by ESI-TOF mass spectrometry and elemental analyses. Crystal structure of 1 characterized with orthorhombic P212121 space group has also been determined.
