Synthesis and Protective Activity of β-Glycosides of <Emphasis Type="Italic">N</Emphasis>-Acetylmuramyl-<Emphasis Type="Italic">L</Emphasis>-Alanyl-<Emphasis Type="Italic">D</Emphasis>-Isoglutamine with Alkylalicyclic and Arylaliphatic Aglycons

The following glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) were synthesized: β-4-tert-butylcyclohexyl MDP, β-2-(adamant-1-yl)ethyl MDP, β-2,2-diphenylethyl MDP, and β-2-(p-biphenyl) ethyl MDP. The starting peracetylated β-N-acetylglucosaminides were prepared by the oxazoline method. They were converted into 4,6-O-isopropylidene-N-acetyl-D-muramic acids, which were coupled with L-Ala-D-Glu(NH₂)OBn. The target glycopeptides were obtained after their deprotection. The stimulation of the anti-infection resistance of mice against Staphylococcus aureus by the MDP glycosides was studied.     

Engineering of <Emphasis Type="Italic">Escherichia coli</Emphasis> for the synthesis of <Emphasis Type="Italic">N</Emphasis>-hydroxycinnamoyl tryptamine and serotonin

Plants synthesize various phenol amides. Among them, hydroxycinnamoyl (HC) tryptamines and serotonins exhibit antioxidant, anti-inflammatory, and anti-atherogenic activities. We synthesized HC–tryptamines and HC–serotonin from several HCs and either tryptamine or serotonin using Escherichia coli harboring the 4CL (4-coumaroyl CoA ligase) and CaHCTT [hydroxycinnamoyl-coenzyme A:serotonin N-(hydroxycinnamoyl)transferase] genes. E. coli was engineered to synthesize N-cinnamoyl tryptamine from glucose. TDC (tryptophan decarboxylase) and PAL (phenylalanine ammonia lyase) along with 4CL and CaHCTT were introduced into E. coli and the phenylalanine biosynthetic pathway of E. coli was engineered. Using this strategy, approximately 110.6 mg/L of N-cinnamoyl tryptamine was synthesized. By feeding 100 μM serotonin into the E. coli culture, which could induce the synthesis of cinnamic acid or p-coumaric acid, more than 99 μM of N-cinnamoyl serotonin and N-(p-coumaroyl) serotonin were synthesized.     

Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates

New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3′-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.     

Species differences and mechanism of action of A<Subscript>3</Subscript> adenosine receptor allosteric modulators

Activity of the A₃ adenosine receptor (AR) allosteric modulators LUF6000 (2-cyclohexyl-N-(3,4-dichlorophenyl)-1H-imidazo [4,5-c]quinolin-4-amine) and LUF6096 (N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarbox-amide) was compared at four A₃AR species homologs used in preclinical drug development. In guanosine 5′-[γ-[³⁵S]thio]triphosphate ([³⁵S]GTPγS) binding assays with cell membranes isolated from human embryonic kidney cells stably expressing recombinant A₃ARs, both modulators substantially enhanced agonist efficacy at human, dog, and rabbit A₃ARs but provided only weak activity at mouse A₃ARs. For human, dog, and rabbit, both modulators increased the maximal efficacy of the A₃AR agonist 2-chloro-N ⁶-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide as well as adenosine > 2-fold, while slightly reducing potency in human and dog. Based on results from N ⁶-(4-amino-3-[¹²⁵I]iodobenzyl)adenosine-5′-N-methylcarboxamide ([¹²⁵I]I-AB-MECA) binding assays, we hypothesize that potency reduction is explained by an allosterically induced slowing in orthosteric ligand binding kinetics that reduces the rate of formation of ligand-receptor complexes. Mutation of four amino acid residues of the human A₃AR to the murine sequence identified the extracellular loop 1 (EL1) region as being important in selectively controlling the allosteric actions of LUF6096 on [¹²⁵I]I-AB-MECA binding kinetics. Homology modeling suggested interaction between species-variable EL1 and agonist-contacting EL2. These results indicate that A₃AR allostery is species-dependent and provide mechanistic insights into this therapeutically promising class of agents.     

Isolation of Natural Naphthoquinones from <Emphasis Type="Italic">Juglans regia</Emphasis> and In Vitro Antioxidant and Cytotoxic Studies of Naphthoquinones and the Synthetic Naphthofuran Derivatives

The naphthoquinones and their derivatives containing hydroxyl group exhibit wide range of pharmacological activities, such as antioxidant, antibacterial, antiviral, anticancer, antimalarial, and antifungal activities. In particular, the antioxidant and anticancer behaviors of these compounds continue to draw attention of researchers. In the present communication, three natural naphthoquinones—juglone, lawsone, and plumbagin—isolated from the chloroform extract of nutshells of Juglans regia Linn. and two 1,4-naphthoquinone derivatives—ethyl-5-hydroxynaphtho[ 1,2-b]furan-3-carboxylate and diethylnaphtho[1,2-b:4,3-b′]difuran-3,4-dicarboxylate—and three 5-hydroxy- 1,4-naphthoquinone derivatives—diethyl-7-hydroxynaphtho[1,2-b:4,3-b']difuran-3,4-dicarboxylate,4-ethoxycarbonyl- 7-hydroxynaphtho[1,2-b:4,3-b']difuran-3-carboxylic acid, and 7-hydroxynaphtho[1,2-b:4,3-b']difuran-3,4- dicarboxylic acid were synthesized and examined for their in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) bioassays. In addition, the cytotoxicity test using human hepatocellular liver carcinoma cell line (HepG2) was carried out for all the compounds. The 5-hydroxy-1,4-naphthoquinone derivatives displayed almost equivalent scavenging activity in DPPH assay and higher activity in ABTS assay relative to ascorbic acid. On the other hand, naphthoquinones Juglone and Plumbagin showed lesser antioxidant activity, but higher cytotoxic activity than naphthofurans except for diethyl naphtho[1,2-b:4,3-b′]difuran-3,4-dicarboxylate, which showed excellent cytotoxic activity.     

Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A

Epothilone A is a derivative of 16-membered polyketide natural product, which has comparable chemotherapeutic effect like taxol. Introduction of sialic acids to these chemotherapeutic agents could generate interesting therapeutic glycoconjugates with significant effects in clinical studies. Since, most of the organisms biosynthesize sialic acids in their cell surface, they are key mediators in cellular events (cell-cell recognition, cell-matrix interactions). Interaction between such therapeutic sugar parts and cellular polysaccharides could generate interesting result in drugs like epothilone A. Based on this hypothesis, epothilone A glucoside (epothilone A 6-O-β-D-glucoside) was further decorated by conjugating enzymatically galactose followed by sialic acids to generate epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactoside i.e., lactosyl epothilone A (lac epoA) and two sialosides of epothilone A namely epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 3″-O-α-N-acetyl neuraminic acid and epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 6″-O-α-N-acetylneuraminic acid i.e., 3′sialyllactosyl epothilone A: 3′SL-epoA, and 6′sialyllactosyl epothilone A: 6′SL-epoA, respectively. These synthesized analogs were spectroscopically analyzed and elucidated, and biologically validated using HUVEC and HCT116 cancer cell lines.     

New furano- and pyrrolo[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine nucleosides and their 5′-<Emphasis Type="Italic">O</Emphasis>-triphosphates: Synthesis and biological properties

Bicyclic furano[2,3-d]pyrimidine ribonucleosides were synthesized by Pd(0)-and CuI-catalyzed coupling of 5-iodouridine with terminal alkynes. The treatment of the resulting nucleosides with ammonia or methylamine solution in aqueous alcohol resulted in pyrrolo-and N ⁷-methylpyrrolo[2,3-d]pyrimidine nucleosides. 5′-O-Triphosphates of bicyclic nucleosides were obtained by the treatment of the nucleosides with POCl₃ in the presence of a “proton sponge.” The 5′-O-triphosphates are not substrates for HCV RNA-dependent RNA polymerase, but are effective substrates for HCV RNA helicase/NTPase and did not inhibit ATP hydrolysis. Only 3-(β-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro-[2,3-d]pyrimidin-2-one showed a moderate anti-HCV activity in the HCV replicon system and efficiently inhibited replication of bovine viral diarrhea virus (BVDV) in KCT-cells, other compounds being inactive. None of the compounds were cytotoxic within the tested range of concentrations.     

Synthesis of some new <Emphasis Type="Italic">N</Emphasis>-substituted-<Emphasis Type="Italic">N</Emphasis>-(2,3-Dihydro-[1,4]benzodioxin-6-yl)-4-acetamidobenzenesulfonamides as valuable antibacterial agents

The aim of the research was to investigate the anti-bacterial potential of some N-substituted sulfonamides bearing benzodioxane moiety. The synthesis was started by reaction of N-2,3-dihydrobenzo[1,4]dioxin-6-amine with 4-acetamidobenzene-1-sulfonyl chloride in the presence of 10% aqueous Na₂CO₃ solution to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-acetamidobenzenesulfonamide, which was further reacted with alkyl/aralkyl halides in DMF and lithium hydride as a base to afford N-substituted-N-(2,3dihydro-[1,4]-benzodioxin-6-yl)-4-acetamidobenzenesulfonamides. All the synthesized compounds were characterized by spectral data (IR, ¹H NMR, EI-MS, and HR-MS). The compounds were tested for antibacterial activity and most of them exhibited potent therapeutic potential against various Gram-negative and Gram-positive strains.     

An efficient method for the sequential production of lipid and carotenoids from the Chlorella Growth Factor-extracted biomass of <Emphasis Type="Italic">Chlorella vulgaris</Emphasis>

Efficient methodology for simultaneous extraction of multiple bioactive compounds from microalgae still remains a major challenge. The present study provides a method for the sequential production of three major products: Chlorella Growth Factor (CGF, a nucleotide-peptide complex enriched with vitamins, minerals, and carbohydrates), lipid, and carotenoids from Chlorella vulgaris biomass in an economically feasible manner. After protein-rich CGF was extracted, the spent biomass was found to contain 12% lipid and 3% carotenoids when extracted individually, compared to that of the un-utilized (fresh) biomass (lipid, 14%; carotenoids, 4%). When extracted simultaneously using conventional methods, the yield of lipid from “CGF and carotenoids-extracted biomass,” and carotenoids from “CGF and lipid-extracted biomass” were significantly reduced (50%). However, simultaneous extraction using different solvent mixtures such as hexane:methanol:water and pentane:methanol:water mixture-augmented lipid yield by 38.5% and carotenoids by 14%, and additionally retained chlorophyll and its derivatives. Column chromatographic approach yielded sequential production of lipid (18%), lutein (9%) with better yields as well as without chlorophyll interference. Different geometric isomers of lutein all-E-(trans)-(3R,3′R,6′R)-β,ε-carotene-3,3′diol, 9Z(cis)-(3R,3′R,6′R)-β,ε-carotene-3,3′diol, and 13Z(cis)-(3R,3′R,6′R)-β,ε-carotene-3,3′diol were purified by HPLC and elucidated by CD, UV, NMR, FT-IR, and Mass spectra. In conclusion, the study provides an efficient and economically viable methodology for sequential production of lipid and lutein along with its geometrical isomers without chlorophyll influence and yield loss from the protein-rich CGF-extracted spent biomass of marine microalga, Chlorella vulgaris.     

Oligonucleotide analogues containing internucleotide C3′-CH<Subscript>2</Subscript>-C(O)-NH-C5′ bonds

A dinucleoside bearing an amide internucleotide C3′-CH₂-C(O)-NH-C5′ bond was synthesized by the interaction of 3′-deoxy-3′-carboxylmethylribothymidine-2′,3′-lactone obtained by hydrolysis of 2′-O-acetyl-5′-O-benzoyl-3′-deoxy-3′-ethoxycarboxylmethylribothymidine with 5′-deoxy-5′-amino-3′-O-(tert-butyldimethylsilyl)thymidine. After standard manipulations with protective groups, the dinucleoside was converted into 3′-O-(2-cyanoethyl-N,N′-diisopropylphosphoroamidite), which was used for the synthesis of modified oligonucleotides on an automatic synthesizer. Duplex melting curves formed by modified and complementary natural oligonucleotides were measured and the melting temperatures and thermodynamic parameters of duplex formation were calculated. The introduction of one modified bond into oligonucleotides caused only an insignificant decrease in the duplex melting temperatures compared with the nonmodified ones.     

Antimicrobial Efficacy of Synthetic Pyranochromenones and (Coumarinyloxy)acetamides

Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls.     

Delineation of the Role of Astroglial GABA Transporters in Seizure Control

Studies of GABA transport in neurons and astrocytes have provided evidence that termination of GABA as neurotransmitter is brought about primarily by active transport into the presynaptic, GABAergic nerve endings. There is, however, a considerable transport capacity in the astrocytes surrounding the synaptic terminals, a transport which may limit the availability of transmitter GABA leading to a higher probability of seizure activity governed by the balance of excitatory and inhibitory neurotransmission. Based on this it was hypothesized that selective inhibition of astrocytic GABA transport might prevent such seizure activity. A series of GABA analogs of restricted conformation were synthesized and in a number of collaborative investigations between Prof. Steve White at the University of Utah and medicinal chemists and pharmacologists at the School of Pharmacy and the University of Copenhagen, Denmark, GABA analogs with exactly this pharmacological property were identified. The most important analogs identified were N-methyl-exo-THPO (N-methyl-3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole) and its lipophilic analog EF-1502 ((RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) both of which turned out to be potent anticonvulsants in animal models of epilepsy.     

Anthelmintic and antibacterial screening of a new series of N-[4-(4-nitrophenoxy)phenyl]-4-(substituted)-1,3-thiazol-2-amines

A series of N-[4-(4-nitrophenoxy)phenyl]-4-(substituted)-1,3-thiazol-2-amines was synthesized. Structural elucidation was accomplished by ¹H NMR, ¹³C NMR, IR, and elemental analyses of synthesized compounds. The title compounds were derived from 4-(4-nitrophenoxy)phenyl thiourea, which is the key intermediate in the synthesis of nitroscanate, an anthelmintic drug. Among the synthesized compounds, N-[4-(4-nitrophenoxy)phenyl]-4-(4-fluorophenyl)-1,3-thiazol-2-amine and N-[4-(4-nitrophenoxy)phenyl]-4-(4-methoxyphenyl)-1,3-thiazol-2-amine exhibited potent anthelmintic and antibacterial activities.     

Synthesis and SAR Studies of Bisthiourea Derivatives of Dipeptides <Emphasis Type="Italic">Lys/lys</Emphasis>-<Emphasis Type="Italic">Asp,Lys/lys</Emphasis>-<Emphasis Type="Italic">Trp</Emphasis> Conjugated Benzo[d]isoxazole as Promising Antioxidants

A novel series of bisthiourea derivatives of four dipeptides consisting of Lys-Asp, lys-Asp, Lys-Trp and lys-Trp conjugated to 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole were synthesized and characterized by physical method and spectroscopic data. The molecules 1–24 were evaluated for their in vitro antioxidant activity and compared with commercial antioxidants ascorbic acid (AA) and gallic acid (GA), employing 1,1-diphenyl-2-picryl-hydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sufonic acid) (ABTS) assays. The results revealed that IC₅₀ of 8, 11, 20 and 23 with electron donating OCH₃ group were lower than the IC₅₀ of commercial standards AA and GA in all the three performed antioxidant assays indicating the good activities of these compounds. The analogues with Trp (13–24) showed better activity than the corresponding analogues with Asp (1–12). Further, the dipeptide derivatives with d-configuration (lys) were found to be more potent than the dipeptide derivatives with l-configuration (Lys).     

Intestinal enterobacteria of the hibernating <Emphasis Type="Italic">Apis mellifera mellifera</Emphasis> L. bees

Dynamics of enterobacteria of normal intestinal microflora was studied in Apis mellifera mellifera L. bees hibernating under snow in the Western Urals. The cell numbers (N) of the predominant species Klebsiella oxytoca increased from 10-10⁶ CFU/bee in November 2004 to 10⁴-10⁷ CFU/bee in March 2005; its frequency of occurrence (P) increased from 92 to 100%. Increase of Providencia rettgeri (11.2004: N up to 10⁶, P 25%; 03.2005: N 10²-10⁶, P 80%) was accompanied by the substitution of Morganella morganii (11.2004: N up to 10⁶, P 25%) with Proteus vulgaris (03.2005: N up to 10⁵, P 8%). By spring, Hafnia alvei and Citrobacter sp., which are pathogenic to bees, disappeared (11.2004: N up to 10⁵, P 13 and 10%, respectively). Endophytic species Pantoea agglomerans, Leclecria sp., and other representatives of the “Enterobacter agglomerans” group were present in November and after the first emergence in spring (N up to 10⁵; November: P 15%; April: P 23%). In April, the number of enterobacteria decreased to 10⁵, and P. rettgeri became the predominant species (P 54%) instead of K. oxytoca (P 43%).     

Acylhydrazones of 20-keto steroids and their transformations: I. Synthesis and properties of 1′-acyl-substituted 3′-methylandrosteno[16,17-<Emphasis Type="Italic">d</Emphasis>]pyrazolines

Acetates of 3β-hydroxy-3′-methyl-1′(N)-acylandrost-5-eno[16,17-d]pyrazolines bearing monothiooxamide acyl groups were synthesized during the study of approaches to the synthesis of 3′-methylandrosteno[16,17-d]azoles, promising biologically active analogues of 20-keto pregnenanes, and their properties were investigated. The cyclization of Δ¹⁶-20-thiooxamidohydrazones to the corresponding heterocycles was shown to proceed under rigorous conditions and to depend partially on the nature of the oxamide grouping.     

Fine-scale differences in genetic and census population size ratios between two stream fishes

Comparing the ratio of effective number of breeders (N _b ) to adult population size (N) among closely related coexisting species can provide insights into the role of life history on N _b /N ratios and inform conservation programs towards limiting the loss of evolutionary potential in natural populations. We estimated N _b and N in two coexisting salmonid fishes (Brook trout and Atlantic salmon) for 3–4 consecutive years in two small, adjacent streams in Newfoundland, Canada, using mark-recapture (N), linkage disequilibrium (N _b(LD)), and sibship frequency approaches (N _b(Sib) ). We found that N _b /N ratios were about 20-fold greater in Atlantic salmon than in brook trout (mean 0.20, range 0.06–0.56 vs. mean 0.02, range 0.01–0.05, respectively). This difference was consistent across N _b estimators. In addition, we found that removing migrants reduced N _b : the strength of the effect was weak for N _b(LD) and much stronger for N _b(Sib). Our results highlight the importance of subtle ecological differences and gene flow in shaping N _b /N. They also provide some evidence that the linkage between demographic and evolutionary processes varies between closely related taxa and suggest that a more complete understanding of the N _b /N range across various species is an important component of conservation genetics and management.     

Interaction of jasmonic acid and blue light in the regulation of arabidopsis morphogenesis

The effects of blue light (BL) and jasmonic acid (JA) on morphogenesis of Arabidopsis thaliana (L.) Heynh seedlings of genotypes Col and Ler and their mutants, namely, axr1-3 and jar1-1 mutants resistant to IAA and JA, respectively, and a CRY1 photoreceptor-deficient mutant hy4 were studied. Both 1 μM JA and BL exposure retarded hypocotyl growth of Ler, Col, and jar1-1 seedlings, whereas JA had no effect on hypocotyl growth of axr1-3, but the suppression of hypocotyl growth of this mutant by BL was even more noticeable than that of Ler, Col, and jar1-1. JA and BL applied simultaneously inhibited hypocotyl growth of axr1-3 and especially of Ler, Col, and jar1-1 more than either of factors applied separately. The hy4 mutant did not respond to BL, whereas JA stimulated its hypocotyl growth. JA did not change the cotyledon size of Col, axr1-3, and jar1-1 and reduced the cotyledon size of Ler and hy4. BL enhanced the cotyledon growth of all wild-type and mutant plants used in the study. The cotyledon sizes of all plants except Ler were also increased when JA and BL were applied together. Some of the growth responses correlated with the endogenous IAA and ABA contents. Thus, for example, the hypocotyl and cotyledon growth retardation of Ler seedlings in the presence of JA correlated with a reduced level of free IAA and a considerable increase in the free ABA level in plants grown both in darkness and in BL. Under other growth conditions, no correlation between the endogenous IAA and ABA levels and A. thaliana seedling growth was noted. The interaction between the signal transduction pathways triggered by BL and JA at the early stages of arabidopsis morphogenesis is discussed on the basis of Col, Ler, axr1-3, and jar1-1 hypocotyl growth responses.     

Synthesis and biological activity of new glycyrrhizic acid conjugates with amino acids and dipeptides

New glycyrrhizic acid (GA) conjugates were synthesized with the use of tert-butyl esters of amino acids or benzyl esters of dipeptides; they contained two residues of L-amino acids (Met, Phe, Pro, and Ile or dipeptides Gly-Leu and Gly-Phe). Activation of GA carboxy groups was carried out with the help of N-hydroxysuccinimide, N,N′-dicyclohexylcarbodiimide, or N-hydroxybenzotriazole with dicyclohexylcarbodiimide. A proline-containing GA derivative is a low-toxic substance; it raises the level of agglutinins by 3.7 times in the blood of mice and 3 times that of hemolysins compared with the control. Dipeptide GA derivatives possess an expressed anti-HIV-1 activity in cultures of MT-4 cells and are 90-70 times less cytotoxic than azidothymidine. The selectivity index of the compounds exceeds those of GA by 110 and 34 times, respectively.     

Synthesis and pharmacological activity of 3-phenoxybenzoic acid derivatives

New esters of N-benzoyl-3-phenoxyphenylcarboxamide acid and N-benzoyl-N′-4-bromophenyl-3-phenoxybenzamidine were synthesized. Some of the synthesized compounds were shown to inhibit the activity of dipeptidyl peptidase-4 and nonenzymatic glycosylation of proteins and manifested antiplatelet and antioxidant properties. The compounds tested did not display the antagonistic effect toward angiotensin II type 1 receptor, did not influence the activity of glycogen phosphorylase and had very little ability to break cross-links of the glycated proteins. The derivatives with the biological activity of two types were found, which can serve as basic molecules in the search for new drug products.