1. AIMS Naphthoquinone and sulfur containing derivatives had been a research subject of much interest due to their antimicrobial, antiviral, anti-inflammatory and antitumor activity. In the present study we describe synthesis, physico-chemical features and antimicrobial activity of new 3-mercapto-2-N- substituted-1,4-naphthoquinones. These derivates of 1,4-naphthoquinone proved good in vitro antibacterial activity against some Gram positive strains and a weak antifungal effect on C. albicans. This encourages further studies regarding the use of these compounds in antibiotic therapy, design of 1,4-naphthoquinones derivates with improved pharmaceutical properties remaining still a research area of the utmost importance. Reagents and solvents used in the present study were of analytical grade and purchased from Merck and Sigma. Elemental analysis has been made on CHNOS Vario El analyzer. Melting points were measured in open capillary tubes with a Gallenkamp melting point apparatus and are uncorrected. UV-Vis spectra were recorded with a Jasco V-530 spectrophotometer, within the range 200–700 nm on substances solved in DMSO. IR spectra have been recorded in KBr pellets with a BioRad FTS 135 FT-IR spectrophotometer, within the range 3500–400 cm -1. For 1 H– NMR spectra a Varian NMR-System 300 spectrometer, at 300 MHz, in CDCl3/DMSO–d6 or DMSO–d6 with TMS as an internal standard was used. Disk diffusion method was used for evaluation of antibacterial activity on Gram-positive and Gram-negative bacterial strains and antifungal activity. SYNTHESIS, PHYSICO-CHEMICAL FEATURES AND ANTIMICROBIAL ACTIVITY OF NEW 3-MERCAPTO-2-N-SUBSTITUTED-1,4-NAPHTHOQUINONES Gabriela Rău 1, Elena Camelia Stănciulescu 2, Anca Berbecaru-Iovan 2, Ana Marina Andrei 2, Flavia Creţu 2, Adela Boroghină 3, Cătălina Gabriela Pisoschi 2 1 I st Department of Pharmacy, 2 II nd Department of Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy Craiova, 3 Clinical Laboratory, Emergency Clinical County Hospital Craiova MATERIAL AND METHODS RESULTS CONCLUSIONS Several 3-mercapto-2-N-substituted 1,4- naphtoquinones were obtained in a two step synthesis starting from dichlone and appropriate N-substituted amino derivates, then treatment of 2-chloro-3-N-substituted-1,4- naphtoquinones with thiourea (Scheme 1). Crude products were purified by recrystallisation from methanol, purity being verified with chromatography. Yields were between 64-83%. All methods confirmed the structure of compounds and their chemical features are presented behind. Chloro and mercapto derivates were active against Gram- positive bacteria Staphylococcus aureus and had a weak antifungal activity on C. albicans (Table 1). Scheme 1 2-chloro-3-(N-thiazol-2-ylamino)-1,4-NQ, 1i - mp. = 164–165 o C, yield = 74%; brown powder; IR ν (cm-1): 3249 (w, NH); 1680 (vi, C=O); 1587,793 (m, m, CH aromatic ring); 1H NMR (CDCl3/DMSO–d6): 4.00 (1H, s, NH); 6.56–7.53 (2H, m, CH thiazole); 7.72–8.00 (4H, m, CH aromatic ring); calc. %: C 53.70; H 2.40; Cl 11.01; N 9.63; S 11.01; found, %: C 53.69; H 2.44; Cl 10.98; N 9.60; S 10.98; C 13 H 7 N 2 O 2 SCl; M = 290.5 g/mol. 4-(2-chloro-3-(N-[4-(1-carboxy-2-hidroxy-phenyl)amino))-1,4-NQ, 2i - mp. = 169.5 o C; yield = 83%,; red-brown powder; IR ν (cm-1): 3254 (w, NH); 1679 (vi, C=O); 3618, 1138 (i, OH); 2921, 1718 (m, i, COOH); 1587, 793 (m, m, CH aromatic ring); 1H NMR (CDCl3/DMSO–d6): 3.98 (1H, s, NH); 4.98 (1H, s, OH); 10.96 (1H, s, COOH); 6.16–7.71 (3H, m, CH aromatic ring), 7.75–8.00 (4H, m, CH aromatic ring); calc.%: C 59.38; H 2.91; Cl 10.33;N 4,07; found, %: C 59.40; H2.92; Cl10.30; N4.18; C 17 H 10 NO 5 Cl;M = 343.5 g/mol. 2-mercapto-3-(N-thiazol-2-ylamino)-1,4-NQ, 1p - mp. = 113.5 o C; yield = 64%; black powder; IR ν (cm-1): 3239 (w, NH); 1685 (vi, C=O); 2567 (w, SH);1586, 795 (m, m, CH aromatic ring); 1H NMR (DMSO–d6): 3.99 (1H, s, NH); 6.56–7.53 (2H, m, CH thiazole); 7.73–8.00 (4H, m, CH aromatic ring); calc. %: C 54.16; H 2.77; N 9.72; S 22.22, found, %: C 54.17; H 2.70; N 9.70; S 22.12; C 13 H 8 N 2 O 2 S 2 ; M = 288 g/mol. 2-mercapto-3-(N-4-(1-carboxy-2-hidroxy-phenyl)amino))-1,4-NQ, 2p-mp. = 101–102 o C; yield = 72%; black powder; IR ν (cm-1): 3256 (w, NH); 1680 (vi, C=O); 2568 (w, SH); 3612, 1209 (i, i, OH); 2922, 1718 (m, i, COOH);1588, 794 (m, m, CH aromatic ring); 1H NMR (DMSO–d6): 3.98 (1H, s, NH);1.50 (1H, s, SH); 4.97 (1H, s, OH);10.95 (1H, s, COOH); 6.18–7.71 (3H, m, CH arom. ring).7.74–8.00 (4H, m, CH arom.ring) calc., %: C 59.82; H 3.22; N 4.10; S 9.38; found, %:C 59.85; H 3.13;N 4.00; S 9.30;C 17 H 11 NO 5 S; M = 341 g/mol Physico-chemical Features Inhibition zone (mm) 1i1i2i2i1p2p DMSOAmp OxaClo S. aureus ATCC ® 25923 21 25 0282020- E. faecalis ATCC ® 29212 111011,51202118- E. coli ATCC ® 25922 0000012-- Klebsiella ATCC®700603 0000011-- C.albicans ATCC®10231 2321 200--28 Table 1 Strains