Abstract: Objective: A series of 2-benzylideneaminonaphthothiazoles were designed and synthesized incorporating the lipophilic naphthalene ring to render them more capable of penetrating various biomembranes. Methods: schiff bases were synthesized by the reaction of naphtha[1,2-d]thiazol-2-amine with various substituted aromatic aldehydes. 2-(2'-Hydroxy)benzylideneaminonaphthothiazole was converted to its Co(II), Ni(II) and Cu(II) metal complexes upon treatment with metal salts in ethanol. All the compounds were evaluated for their antibacterial activities by paper disc diffusion method with Gram positive Staphylococcus aureus and Staphylococcus epidermidis and Gram negative Escherichia coli and Pseudomonas aeruginosa bacteria. The minimum inhibitory concentrations of all the schiff bases and metal complexes were determined by agar streak dilution method. Results: All the compounds moderately inhibited the growth of Gram positive and Gram negative bacteria. In the present study among all schiff bases 2-(2'-hydroxy)benzylideneaminonaphthothiazole showed maximum inhibitory activity and among metal complexes Cu(II) metal complex was found to be most potent. Conclusion: The results obtained validate the hypothesis that schiff bases having substitution with halogens, hydroxyl group and nitro group at phenyl ring are required for the antibacterial activity while methoxy group at different positions in the aromatic ring has minimal role in the inhibitory activity. The results also indicated that the metal complexes are better antibacterial agents as compared to the schiff bases.

[1] Alvarez, S., Julve, M., Verdaguer, M., 1990. Oxalato-bridged and related dinuclear copper(II) complexes—theoretical analysis of their structures and magnetic coupling. Inorg. Chem., 29(22):4500-4507.

[2] Amir, M., Azam, F., 2004a. Synthesis and biological evaluation of some 4-thiazolidinones. Indian J. Het. Chem., 14(2):119-122.

[3] Amir, M., Azam, F., 2004b. Synthesis and antimicrobial activities of some 5-(4'-pyridyl)-4-substituted benzy-lideneamino-3-mercapto(4H)-1,2,4-triazoles. Indian J. Pharm. Sci., 66(6):818-821.

[4] Aydogan, F., Öcal, N., Turgut, Z., Yolacan, C., 2001. Transformations of aldimines derived from pyrrole-2-carboxaldehyde. Synthesis of thiazolidino-fused compounds. Bull. Korean Chem. Soc., 22(5):476-480.

[5] Bosnich, B., 1968. An interpretation of circular dichroism and electronic spectra of salicylaldimine complexes of square-coplanar diamagnetic nickel(II). J. Am. Chem. Soc., 90(3):627-632.

[6] Cervera, B., Ruiz, R., Lloret, F., Julve, M., Cano, J., Faus, J., Bois, C., Mrozinski, J., 1997. Tuning the nature of the exchange interaction in out-of-plane oximato-bridged dinuclear copper(II) complexes. J. Chem. Soc. Dalton Trans., 3:395-402.

[7] Chohan, Z.H., Scozzafava, A., Supuran, C.T., 2003. Zinc complexes of benzothiazole-derived Schiff bases with antibacterial activity. J. Enzyme Inhib. Med. Chem., 18(3):259-263.

[8] Desai, S.B., Desai, P.B., Desai, K.R., 2001. Synthesis of some Schiff bases, thiazolidones, and azetidinones derived from 2,6-diaminobenzo[1,2-d:4,5-d′]bisthiazole and their anticancer activities. Heterocycl. Commun., 7(1):83-90.

[9] El-Ayaan, U., Abdel-Aziz, A.A.M., 2005. Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: bis [N-(2,6-diisopropylphenyl)imino] acenaphthene. Eur. J. Med. Chem., 40(12):1214-1221.

[10] El-Masry, A.H., Fahmy, H.H., Abdelwahed, S.H.A., 2000. Synthesis and antimicrobial activity of some new benzimidazole derivatives. Molecules, 5(12):1429-1438.

[11] Erwin, B., Omoshile, C., 1995. Hydrogen isotope-exchange in Pt-II-thiazole complexes. J. Chem. Soc. Perkin Trans., 7:1333-1338.

[12] Fioravanti, R., Biaval, M., Porrettal, G.C., Landolfil, C., Simonetti, N., Villa, A., Conte, E., Puglia, A.P., 1995. Research on antibacterial and antifungal agents. XI. Synthesis and antimicrobial activity of N-heteroaryl benzylamines and their Schiff bases. Eur. J. Med. Chem., 30(2):123-132.

[13] Geronikaki, A., Hadjipavlou-Litina, D., Amourgianou, M., 2003. Novel thiazolyl, thiazolinyl and benzothiazolyl Schiff bases: a possible lipoxygenase’s inhibitors and anti-inflammatory agents. IL Farmaco, 58(7):489-495.

[14] Harbarth, S., Albrich, W., Goldmann, D.A., Huebner, J., 2001. Control of multiply resistant cocci: do international comparisons help? Lancet Infect. Dis., 1(4):251-261.

[15] Lau, K.Y., Mayr, A., Cheung, K.K., 1999. Synthesis of transition metal isocyanide complexes containing hydrogen bonding sites in peripheral locations. Inorg. Chim. Acta, 285(2):223-232.

[16] Luthra, P.M., Singh, S., Azam, F., 2006. Synthesis of 2-Benzylidineaminonaphthothiazoles as Potential Antibacterial Agents. Joint International Conference on Building Bridges, Forging Bonds for 21st Century Organic Chemistry and Chemical Biology (ACS-CSIR-OCCB 2006). Jan. 6-9, National Chemical Laboratory, Pune, India.

[17] Maass, G.I.U., Koenig, B., Leser, U., Mueller, B., Goody, R., Pfatt, B., 1993. Viral resistance to the thiazole isoindolinones, a new class NNRTI of HIV-1 reverse transcriptase. Antimicrob. Agents. Chemother., 37(12):2612-2617.

[18] Mehra, S.C., Zaman, S., 1978. Synthesis of some local anaesthetics from 2-aminonaphthothiazole. J. Chem. Eng. Data, 23(1):89-90.

[19] Mitscher, L.A., Pillai, S.P., Gentry, E.J., Shankel, D.M., 1999. Multiple drug resistance. Med. Res. Rev., 19(6):477-496.

[20] Nakamura, A., Konushi, A., Otsuka, S., 1979. Chiral metal complexes. Part 5. Cobalt(II) chiral vic-dioximate ligands derived from D-camphor and L-β-pinene. J. Chem. Soc. Dalton Trans., 3:488-495.

[21] Pandeya, S.N., Sriram, D., Nath, G., de Clercq, E., 1999. Synthesis and antimicrobial activity of Schiff and Mannich bases of isatin and its derivatives with pyrimidine. IL Farmaco, 54(9):624-628.

[22] Panico, A.M., Geronikaki, A., Mgonzo, R., Cardile, V., Gentile, B., Doytchinova, I., 2003. Aminothiazole derivatives with on cartilage. Bioorg. Med. Chem., 11(13):2983-2989.

[23] Samadhiya, S., Halve, A., 2001. Synthetic utility of Schiff bases as potential herbicidal agents. Orient. J. Chem., 17(1):119-122.

[24] Schrauzer, G.N., Kohnle, J., 1964. Co-enzyme B12-modelle. Chem. Ber., 97(11):3056-3064.

[25] Singh, W.M., Dash, B.C., 1998. Synthesis of some new Schiff bases containing thiazole and oxazole nuclei and their fungicidal activity. Pesticides, 22(11):33-37.

[26] Sonmez, M., Berber, I., Akbas, E., 2006. Synthesis, antibacterial and antifungal activity of some new pyridazinone metal complexes. Eur. J. Med. Chem., 41(1):101-105.

[27] Tandon, V.K., Yadav, D.B., Singh, R.V., Vaish, M., Chaturvedi, A.K., Shukla, P.K., 2005. Synthesis and biological evaluation of novel 1,4-naphthoquinone derivatives as antibacterial and antiviral agents. Bioorg. Med. Chem. Lett., 15(14):3463-3466.

[28] Trávníček, Z., Maloň, M., Šindelář, Z., Doležal, K., Rolčik, J., Kryštof, V., Strnad, M., Marek, J., 2001. Preparation, physicochemical properties and biological activity of copper(II) complexes with 6-(2-chlorobenzylamino) purine (HL) or 6-(3-chlorobenzylamino)purine (HL). The single-crystal X-ray structure of [Cu(H⁺L₂)₂Cl₃]Cl·2H₂O. J. Inorg. Biochem., 84(1-2):23-32.

[29] Vicini, P., Geronikaki, A., Incerti, M., Busonera, B., Poni, G., Cabras, C.A., La Colla, P., 2003. Synthesis and biological evaluation of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases. Bioorg. Med. Chem., 11(22):4785-4789.

[30] West, B.O., 1962. The Magnetic moments and structure of some N-substituted salicylideneimine complexes of cobalt(II). J. Chem. Soc., p.1374-1378.

[31] Wu, C.Y., Chen, L.H., Hwang, W.S., Chen, H.S., Hung, C.H., 2004. Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethyli-dene)-2-thiolethylamine. J. Organomet. Chem., 689(13):2192-2200.