OBJECTIVEA natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapeptide units Boc-Leu-Pro-Trp-Leu-OMe and Boc-Ile-Ala-Ala-Gly-OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear octapeptide segment.

METHODSSolution phase technique was adopted for the synthesis of cyclooctapeptide-sarcodactylamide. Required tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc-Leu-Pro-OH and Boc-Ile-Ala-OH with respective dipeptide methyl esters Trp-Leu-OMe and Ala-Gly-OMe. Cyclization of linear octapeptide unit was done by p-nitrophenyl ester method. The structure of synthesized cyclopolypeptide was elucidated by FTIR, 1H NMR, 13C NMR, FABMS spectral data and elemental analysis. The newly synthesized peptide was evaluated for different pharmacological activities including antimicrobial, anthelmintic and cytotoxic activities.

RESULTSSynthesis of sarcodactylamide was accomplished with >78% yield utilizing dicyclohexylcarbodiimide (DCC) as coupling agent. Newly synthesized peptide possessed potent cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines, in addition to moderate anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus sp. Moreover, cyclopolypeptide displayed good antimicrobial activity against pathogenic fungi Candida albicans and Gram-negative bacteria Pseudomonas aeruginosa, in comparison to standard drugs griseofulvin and ciprofloxacin.

CONCLUSIONSolution phase technique employing DCC and triethylamine (TEA) as base proved to be effective for the synthesis of natural cyclooctapeptide. N-methyl morpholine (NMM) was found to be a better base for the cyclization of linear octapeptide unit in comparison to TEA and pyridine.

Animals ; Anti-Infective Agents ; chemical synthesis ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Citrus ; chemistry ; Mice ; Peptides, Cyclic ; chemical synthesis ; pharmacology

Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.
Anti-Infective Agents ; chemical synthesis ; chemistry ; Antimicrobial Cationic Peptides ; chemical synthesis ; chemistry ; Drug Design ; Inhibitory Concentration 50 ; Macromolecular Substances ; chemical synthesis ; chemistry ; Polymers ; chemical synthesis ; chemistry

A total of 62 leprosy patients, 47 lepromatous type, 9 tuberculoid, 5 borderline group and 1 indeterminate group, have been treated with a synthesized thiocarbanilide L-4, and the effectiveness of L-4 administration in the treatment of leprosy is evaluated on the basis of clinical and bacteriological improvements. The results are summarized and conc1uded as follows; 1. L-4, contained in gelatin capsule, can be safely administered orally to the patients through slow induction, from initial dosages of 50 mg to 100 mg dai1y to the therapeutic maintenance levels of 200 mg to 300 mg daily, for a period of time. 2. L-4 administration has brought apparent and remarkable improvement in clinical symptoms of the patients after a relatively short period of medication compared with that of DDS administration. 3. Changes of SFG values caused by L-4 administration were much speedier than, (or, at least, equivalent to) the effect caused by DDS. The changes of SFG values, in general, synchronized fairly well with clinical improvement of the patients. 4. Lepromatous cases with leprosy reaction or sulfone allergy responded well to L-4 medication with remarkable clinical improvement, and prolonged administration of L-4 did not provoke such a precipitating action to leprosy reaction as did DDS.
Adolescent ; Adult ; Anilides/chemical synthesis ; Anilides/therapeutic use* ; Anti-Infective Agents/chemical synthesis ; Anti-Infective Agents/therapeutic use* ; Child ; Female ; Human ; Leprosy/drug therapy* ; Male ; Middle Age ; Sulfur*

Mytilin-derived-peptide-1 (MDP-1) and mytilin-derived-peptide-2 (MDP-2) are two truncated decapeptides with reversed sequence synthesized corresponding to the residues 20-29 of mytilin-1 (GenBank Accession No. FJ973154) from M. coruscus. The objective of this study is to characterize the structural basis of these two peptides for their antimicrobial activities and functional differences, and to investigate the inhibitory mechanism of MDPs on Escherichia coli and Sarcina lutea. The structures of MDP-1 and MDP-2 in solution were determined by 1H 2D NMR methods; the antibactericidal effects of MDPs on E. coli and S. lutea were observed by transmitted electron microscopy (TEM). Both MDP-1 and MDP-2 have a well-defined loop structure stabilized by two additional disulfide bridges, which resemble the-hairpin structure of mytilin-1 model. The surface profile of MDPs' structures was characterized by protruding charged residues surrounded by hydrophobic residues. TEM analysis showed that MDPs destroyed cytoplasmic membrane and cell wall of bacteria and the interface between the cell wall and membrane was blurred. Furthermore, some holes were observed in treated bacteria, which resulted in cell death. Structural comparison between MDP-1 and MDP-2 shows that the distribution of positively charged amino acids on the loop of MDPs is topologically different significantly, which might be the reason why MDP-2 has higher activity than MDP-1. Furthermore, TEM results suggested that the bactericidal mechanisms of MDPs against E. coli and S. lutea were similar. Both MDP-1 and MDP-2 could attach to the negatively charged bacterial wall by positively charged amino acid residues and destroy the bacteria membrane in a pore-forming manner, thus cause the contents of the cells to release and eventually cell death.
Animals ; Anti-Infective Agents ; chemical synthesis ; pharmacology ; Antimicrobial Cationic Peptides ; chemical synthesis ; chemistry ; pharmacology ; Cell Wall ; drug effects ; Escherichia coli ; drug effects ; Mytilus ; chemistry ; Sarcina ; drug effects

As a key role in mussel defense system, Mytilin is an important antibacterial peptide isolated from the mussel serum. The structural and functional researches on Mytilin showed that the fragment connecting two beta-sheets in a stable beta-hairpin structure was probably required for antimicrobial activity. To elucidate the structural features and the antimicrobial activity of this fragment, we re-designed and synthesized two peptides corresponding to the main mimic structures of Mytilin-1 from Mytilus coruscus, we named these two peptides Mytilin Derived Peptide-1 and Mytilin Derived Peptide-2, respectively. Using a liquid growth inhibition assay, we evaluated their activity towards Gram-positive, Gram-negative bacteria and fungus. The results showed that both peptides can inhibit the growth of Gram-positive, Gram-negative bacteria and fungus. Besides, these two peptides showed high stability in heat water and human serum. These works laid the foundation for further research on the molecular mechanism of Mytilin and for further exploitation of antibacterial peptides with lower molecular mass and more stable structure.
Amino Acid Sequence ; Animals ; Anti-Infective Agents ; chemical synthesis ; pharmacology ; Antimicrobial Cationic Peptides ; chemical synthesis ; chemistry ; pharmacology ; Molecular Sequence Data ; Mytilus ; chemistry

AIMTo study the synthesis and antibacterial activity of ciprofloxacin derivatives.

METHODSCiprofloxacin derivatives were synthesized primarily from 2-methyl-5-nitroimidazol and ciprofloxacin through nucleophilic substitution. The antibacterial activity of the synthesized compounds were tested.

RESULTSNine new compounds were synthesized. The structure of the title compounds were confirmed by 1H NMR, MS and element analysis.

CONCLUSIONCompounds II, IVC and IVD showed appreciable antibacterial activity, and were worth further studying.

Animals ; Anti-Infective Agents ; chemical synthesis ; chemistry ; pharmacology ; Ciprofloxacin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Female ; Mice ; Molecular Structure ; Nitroimidazoles

AIMTo synthesize new fluoroquinolone analogues as antibacterial compounds.

METHODS AND RESULTSBy reaction of acryl chloride(chloro-carbonic ester) with sodium sulfocyanate, acyl isosulfocyanic ester were easily obtained. Twelve 7-(4-acylamino-thiocarbamoyl-1-piperazinyl) fluoroquinolone analogues (1-12) were synthesized through modifying the 7-piperazine of norflorxacin and ciprofloxacin with isosulfocyanic ester synthesized above. The structures of synthesized compounds were characterized by 1HNMR, IR and elemental analysis.

CONCLUSIONAntibacterial activities of the new compounds were evaluated in vitro compared with norflorxacin. Compounds 5, 7, 10 and 12 showed antibacterial activities.

Anti-Infective Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Ciprofloxacin ; chemistry ; pharmacology ; Combinatorial Chemistry Techniques ; methods ; Escherichia coli ; drug effects ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; Microbial Sensitivity Tests ; Molecular Structure ; Norfloxacin ; chemistry ; pharmacology

AIMTo study the synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol.

METHODSPyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol were synthesized primarily from 2-methyl-5-nitroimidazol, norfloxacin, ciprofloxacin, enoxacin via nucleophilic substitution and esterification. The antibacterial activity of the nine target compounds were tested.

RESULTSNine new compounds were synthesized (IIa-c and IIIa-f). The structure of the title compounds were identified by 1HNMR, MS as well as elementary analysis.

CONCLUSIONCompounds IIa, IIb and IIc showed antibacterial activity, and were worth further studying.

Animals ; Anti-Infective Agents ; chemical synthesis ; chemistry ; pharmacology ; Ciprofloxacin ; antagonists & inhibitors ; chemical synthesis ; pharmacology ; Combinatorial Chemistry Techniques ; methods ; Enoxacin ; antagonists & inhibitors ; chemical synthesis ; pharmacology ; Escherichia coli ; drug effects ; Female ; Mice ; Microbial Sensitivity Tests ; Molecular Structure ; Nitroimidazoles ; chemistry ; Norfloxacin ; antagonists & inhibitors ; chemical synthesis ; pharmacology

OBJECTIVETo prepare the controlled-release delivery gutta-percha points containing metronidazole compound (CDGMC) and to determine its release rate in vitro.

METHODSThe drug points were made by using compound drugs and gutta-percha as a carrier, and CDGMC were prepared followed by enveloping a release membrane outward. The best formula was selected according to the release parameters of the drugs extracted in the release experiments in vitro. The CDGMC were placed into the extracted teeth after root canals were routinely prepared. The non-drug CDGMC was used as the control. The absorbency of the drugs in normal saline (37 degrees C, pH 7.4) was determined timely. The percentage of release and cumulated release of the drugs were calculated according to the concentrations of drugs in medium.

RESULTSThe in vitro experiments showed that this system contained 1,880 micrograms of metronidazole and 267 micrograms of ciprofloxacin. The experiments in healthy single root canal showed that the drug release amounts around the perioapical area were metronidazole 88.54 micrograms/ml and ciprofloxacin 9.05 micrograms/ml in 10 days.

CONCLUSIONCDGMC can continuously release effective drug concentrations more than 10 days and could be considered as an ideal method for clinical application.

Anti-Infective Agents, Local ; administration & dosage ; pharmacokinetics ; Ciprofloxacin ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; chemical synthesis ; pharmacokinetics ; Dental Pulp Cavity ; drug effects ; metabolism ; Drug Delivery Systems ; Gutta-Percha ; Humans ; Metronidazole ; administration & dosage ; pharmacokinetics ; Root Canal Therapy ; methods

OBJECTIVETo synthesize silver nanopaticles from leaves extract of Eucalyptus chapmaniana (E. chapmaniana) and test the antimicrobial of the nanoparticles against different pathogenic bacteria, yeast and its toxicity against human acute promyelocytic leukemia (HL-60) cell line.

METHODSTen milliliter of leaves extract was mixed with 90 mL of 0.01 mmol/mL or 0.02 mmol/mL aqueous AgNO3 and exposed to sun light for 1 h. A change from yellowish to reddish brown color was observed. Characterization using UV-vis spectrophotometery and X-ray diffraction analysis were performed. Antimicrobial activity against six microorganisms was tested using well diffusion method and cytoxicity test using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole was obtained on the human leukemia cell line (HL-60).

RESULTSUV-vis spectral analysis showed silver surface plasmon resonance band at 413 nm. X-ray diffraction showed that the particles were crystalline in nature with face centered cubic structure of the bulk silver with broad beaks at 38.50° and 44.76°. The synthesized silver nanoparticles efficiently inhibited various pathogenic organisms and reduced viability of the HL-60 cells in a dose-dependent manner.

CONCLUSIONSIt has been demonstrated that the extract of E. chapmaniana leaves are capable of producing silver nanoparticles extracellularly and the Ag nanoparticles are quite stable in solution. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial and anticancer activity of these particles.

Anti-Infective Agents ; chemical synthesis ; pharmacology ; toxicity ; Bacteria ; drug effects ; Candida albicans ; drug effects ; Cell Line, Tumor ; Eucalyptus ; chemistry ; Humans ; Metal Nanoparticles ; chemistry ; toxicity ; Plant Extracts ; chemistry ; pharmacology ; toxicity ; Plant Leaves ; chemistry ; Silver ; pharmacology ; toxicity