ANTIBACTERIAL, ANTIVIRAL, ANTITUMOR, AND ANTIOXIDANT ACTIVITIES OF SOME PYRIMIDINE COMPOUNDS

Abstract

The values of the biological determinations of six pyrimidine derivatives, phenyl-substituted with (1) 3-OH; (2) 2-OH, 3-OCH;; (3) 2-CI; (4) 4-C1; (5) 3-CI; (6) 2-naphthyl, which were synthesized in the laboratory and characterized physico-chemically, were compared with of the same results for the unsubstituted phenyl structural control. The antioxidant activity was determined by the ABTS method and the results were expressed as chlorogenic acid equivalents g/g compound. Antioxidant activity values of the derivatives do not significantly differ and are close to the value calculated for the compound with unsubstituted phenyl.

Objectives. The study objective is to determine the antibacterial, antiviral, antitumor and antioxidant activities of some dihydropyrimidine compounds.

Materials and methods. The values of the biological determinations of six pyrimidine derivatives, phenyl-substituted with (1) 3-OH; (2) 2-OH, 3-OCH;; (3) 2-CI; (4) 4-C1; (5) 3-CI; (6) 2-naphthyl, which were synthesized in the laboratory and characterized physico-chemically, were compared with of the same results for the unsubstituted phenyl structural control. To determine the antimicrobial activity of the compounds, the diffusimetric antibiogram method was adapted, using reference strains: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Antiviral activity screening was performed on HeLa cells, adapting the SR EN 14476+A2 standard. The MTT method, normal human fibroblast cell line, was used for cytotoxicity analysis. The antioxidant activity was determined by the ABTS method and the results were expressed as chlorogenic acid equivalents g/g compound.

Results and discussion. The compounds had an antibacterial effect on the Ps. aeruginosa strain. The E. coli strain was less sensitive; S. aureus strain was resistant. The cellulose disc technique revealed resistance for all bacteria. Quantifiable results were obtained with the cylinder technique where a larger volume (100 uL) of compound solution was used. Good antibacterial activities were shown by derivatives (1), (4), and (6), which also had cell viability over 70 %. The tested pyrimidine derivatives inhibited virus replication in cells by at most about 1 lg half. Derivatives (6), (2), and (4) proved to be the most potent compunds. Antioxidant activity values of the derivatives do not significantly differ and are close to the value calculated for the compound with unsubstituted phenyl.

Conclusion. Derivatives (1) and (6) are good candidates for the functionalization of hydrogels with topical administration and antimicrobial activity.

Funding: This work is financed by the Ministry of National Defense through the PSCD project ,,Innovative pharmaceutical preparations with topical administration and antimicrobial activity based on new synthetic hybrid compounds ".

Obiective. Obiectivul studiului este determinarea activitátilor antibacteriene, antivirale, antitumorale si antioxidante ale unor compusi dihidropirimidinici.

Materiale si metode. Valorile determinárilor biologice a şase derivati pirimidinici, fenilsubstituiti cu (-3 (10H, (-2 (20H si -30CH,; (3) 2-CI, (4) 4-CI, (5) 3-CI si (6) 2-naftil, sintetizati in laborator si caracterizati fizico-chimic, au fost comparate cu rezultatele acelorasi determinäri pentru martorul structural fenil nesubstituit. Pentru determinarea activitátii antimicrobiene a compusilor a fost adaptatá metoda antibiogramei difuzimetrice, folosind tulpini de referintá: Staphylococcus aureus, Escherichia coli si Pseudomonas aeruginosa. Screening-ul activitätii antivirale s-a efectuat pe celule HeLa, adaptandu-se standardul SR EN 14476+A2. Pentru analiza citotoxicitatii s-a folosit metoda MTT, linie celulara fibroblaste umane normale. Activitatea antioxidanta a fost determinata prin metoda ABTS, iar rezultatele exprimate in echivalenti acid clorogenic g/g compus.

Rezultate si discutii. Compusii testati au avut efect antibacterian asupra tulpinii de Ps. aeruginosa. Tulpina de E. coli a fost mai putin sensibila, iar S. aureus - rezistentä. Tehnica pe disc de celuloza a relevat rezistenta pentru toate bacteriile. Au fost obtinute rezultate cuantificabile la tehnica in cilindru unde s-a utilizat un volum mai mare de solutie cu compus (100 pL). Activitate antibacterianá buna au prezentat derivatii (1), (4) si (6), care au si viabilitate celulard peste 70 %. Compusii testati au inhibat replicarea virusurilor in celule cu cel mai mult aproximativ 11g jumatate. Derivatii (6), (2) si (4) s-au remarcat ca fiind cei mai potenti. Valorile activitatii antioxidante ale derivatilor analizati nu diferá semnificativ si sunt apropiate de valoarea calculatá pentru compusul cu fenil nesubstitut.

Concluzii. S-au remarcat derivatii (1) si (6), ei fiind candidati buni pentru functionalizarea unor hidrogeluri cu administrare topicá si activitate antimicrobianá.

Sursa de finantare: Aceastá lucrare este finantatá de Ministerul Apdrarii Nationale prin proiectul PSCD ,, Preparate farmaceutice inovative cu administrare topicá si activitate antimicrobiana pe bazá de noi compusi de sintezá hibrizi ".

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*Corresponding author: Claudia Valentina Popa, e-mail: [email protected], valentina.popa@ chimie.unibuc.ro