Immunosuppressive properties of amino acid and peptide derivatives of mycophenolic acid

Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as immunosuppressant, it possesses also anticancer activity. MPA acts as Inosine-5’-Monophosphate Dehydrogenase (IMPDH) inhibitor, where carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the other hand, potent anticancer agents like dacarbazine and cisplatin give numerous side-effects. Objective: Based on the literature data, MPA derivatives should be explored towards anticancer properties. Conversion of carboxylic group of MPA to amide could maintain antiproliferative activity. Therefore, we decided to investigate several amino acid and peptide derivatives of MPA against chosen cancer cell lines in vitro. Methods: Amides of MPA hold threonine and arginine amino acid unit. These amino acid derivatives were tested as L and D enantiomers and both in free acid and methyl esters forms. Additionally, MPA was modified with tuftsin or retro-tuftsin as biologically active peptides, which could act as a drug carrier. Results: Amino acid and peptide derivatives of MPA were investigated in vitro as potential anticancer agents on cell lines: Ab melanoma, A375 melanoma and SHSY5Y neuroblastoma. The activity of the tested compounds was compared to parent MPA and known chemotherapeutics: dacarbazine and cisplatin. Conclusion: Amino acid moiety and sequence of amino acids in peptide part influenced observed activity. The most active amino acid MPA analogues occurred to be D and L-threonine derivatives as methyl esters, probably due to better cell membrane penetration.

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SYNTHESIS AND ANTIMICROBIAL EVALUATION OF QUINAZOLINONE PEPTIDE DERIVATIVES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10s4.21329 ◽

2017 ◽

Vol 10 (16) ◽

pp. 7 ◽

Cited By ~ 2

Author(s):

Bhupinder Kapoor ◽

Arshid Nabi ◽

Reena Gupta ◽

Mukta Gupta

Keyword(s):

Antibacterial Activity ◽

Amino Acid ◽

Antimicrobial Agents ◽

Methyl Esters ◽

Standard Drug ◽

Amino Acid Peptide ◽

Chemical Structures ◽

1H Nuclear Magnetic Resonance ◽

Peptide Derivatives ◽

Derivatives Of

Objective: The increased microbial resistance against commercially available drugs initiated the development of novel and safe antimicrobial agents in last few decades. In this view, a series of amino acid/dipeptide derivatives of quinazolin-3(4H)-one was synthesized and was evaluated for their antimicrobial potential.Method: Synthesis of amino acid/peptide derivatives were carried out by coupling 5-(2-(2-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-2-hydroxy benzoic acid with amino acid/dipeptide methyl esters in the presence of dicyclohexylcarbodiimide and N-methylmorpholine. The chemical structures of synthesized compounds were characterized by 1H nuclear magnetic resonance and infrared spectroscopy and were screened for antibacterial activity by disc diffusion method.Results: All the synthesized derivatives exhibited moderate to significant antibacterial activity against both Gram-positive and Gram-negative bacteria. The potency of compound 5d was comparable to standard drug ciprofloxacin in all the strains of bacteria used. The compound 5a was found to be more active against Streptococcus pyogenes and Staphylococcus aureus while compound 5c against Pseudomonas aeruginosa and Escherichia coli. Conclusion: Peptide derivatives of quinazolinone are promising antimicrobial agent and can be used for the synthesis of other novel compounds.

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Amino Acid and Peptide Derivatives of Kojic Acid and Their Antifungal Properties

Agricultural and Biological Chemistry ◽

10.1080/00021369.1990.10870342 ◽

1990 ◽

Vol 54 (9) ◽

pp. 2441-2442

Author(s):

Hiroshi Kayahara ◽

Norihisa Shibata ◽

Koji Tadasa ◽

Hideo Maeda ◽

Takashi Kotani ◽

...

Keyword(s):

Amino Acid ◽

Kojic Acid ◽

Antifungal Properties ◽

Peptide Derivatives ◽

Derivatives Of

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Synthesis and Antimicrobial and Toxicological Studies of Amino Acid and Peptide Derivatives of Kanamycin A and Netilmicin

Journal of Medicinal Chemistry ◽

10.1021/jm00023a011 ◽

1995 ◽

Vol 38 (23) ◽

pp. 4710-4719 ◽

Cited By ~ 23

Author(s):

S. Kotretsou ◽

M. P. Mingeot-Leclercq ◽

V. Constantinou-Kokotou ◽

R. Brasseur ◽

M. P. Georgiadis ◽

...

Keyword(s):

Amino Acid ◽

Toxicological Studies ◽

Peptide Derivatives ◽

Derivatives Of

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Dependence of the degree of association of water-soluble amino acid and peptide derivatives of fullerene[60] on pH and the ionic strength of a solution

Russian Chemical Bulletin ◽

10.1007/bf02495397 ◽

1997 ◽

Vol 46 (3) ◽

pp. 472-475 ◽

Cited By ~ 13

Author(s):

G. I. Timofeeva ◽

E. F. Kuleshova ◽

V. S. Romanova

Keyword(s):

Amino Acid ◽

Ionic Strength ◽

Water Soluble ◽

Peptide Derivatives ◽

Degree Of Association ◽

Derivatives Of

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Synthesis and properties of peptidyl derivatives of arginylfluoromethanes

Biochemical Journal ◽

10.1042/bj2560481 ◽

1988 ◽

Vol 256 (2) ◽

pp. 481-486 ◽

Cited By ~ 21

Author(s):

H Angliker ◽

P Wikström ◽

P Rauber ◽

S Stone ◽

E Shaw

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Active Site ◽

Relative Effectiveness ◽

Serine Proteinases ◽

Cysteine Proteinases ◽

Peptide Derivatives ◽

Guanidino Group ◽

Derivatives Of

Two peptide derivatives of arginylfluoromethane (Arg-CH2F), namely Bz(benzoyl)-Phe-ArgCH2F and D-Phe-Pro-Arg-CH2F, have been synthesized by extension of available methods, i.e. the Dakin-West reaction [Rasnick (1985) Anal. Biochem. 149, 461-465] or synthesis of a phthaloyl-blocked C-terminal fluoromethane [Rauber, Angliker, Walker & Shaw (1986) Biochem. J. 239, 633-640; Angliker, Wikström, Rauber & Shaw (1987) Biochem. J. 241, 871-875] with subsequent elongation. The guanidino group of arginine was protected as the bis-Cbz (benzyloxycarbonyl) derivative. The products were examined as active-site-directed inhibitors of some trypsin-related serine proteinases as well as a pair of cysteine proteinases. The results extend previous observations that the rate of alkylation of serine proteinases by fluoromethanes may be considerably slower than by chloromethanes. As expected, the amino acid sequence of the inhibitors influenced their relative effectiveness. Thus the rate of inactivation of a number of trypsin-like proteinases by D-Phe-Pro-Arg-CH2F varied by more than two orders of magnitude.

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