Synthesis, Reactions and Antimicrobial Activity of Some New 3-Substituted Indole Derivatives

Asmaa S. Salman^1*, Naema A. Mahmoud¹, Anhar Abdel-Aziem¹, Mona A. Mohamed², Doaa M. Elsisi¹

¹Department of Chemistry, Faculty of Science, Al-Azhar University, Girls’ Branch, Nasr City, Cairo, Egypt.
²Biochemistry Division, Faculty of Science, Al-Azhar University, Girls’ Branch, Nasr City, Cairo, Egypt.

DOI: 10.4236/ijoc.2015.52010                

Abstract

Reaction of indole-3-carboxaldehydes 4 with hydrazine derivatives and different substituted acid hydrazides afforded the corresponding hydrazine derivatives 5a-c and acid hydrazide derivatives 7-11 respectively. Condensation of indole-3-carboxaldehydes 4 with phenacyl bromide and thiourea gives 1,3-thiazol-2-amine derivative 18. On the other hand, reaction 4 with 3-acetylchromene-2-one afforded chalcone derivative 19. Compound 4 undergoing Knoevenagel condensation with cyanoacetamide, ethyl cyanoacetate, benzimidazol-2-ylacetonitrile, rhodanine-3-acetic acid, 2,3-dihydropyrimidin-4-one derivative and 2,4-dihydropyrazol-3-one afforded the compounds 20a,b, 22, 23, 27 and 28 respectively. The structure of the newly synthesized compounds has been confirmed by elemental analysis and spectra data. The antimicrobial activities of the some newly synthesized compounds were measured and showed that most of them have high activities

Keywords

Indole-3-Carboxaldehyde, Acid Hydrazide, 1, 3-Thiazole, Pyrimidine, Antimicrobial

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Nagai, K., Davies, T.A., Jacobs, M.R. and Appelbaum, P.C. (2002) Effects of Amino Acid Alterations in Penicillin-Binding Proteins (Pbps) 1a, 2b, and 2× on PBP Affinities of Penicillin, Ampicillin, Amoxicillin, Cefditoren, Cefuroxime, Cefprozil, and Cefaclor in 18 Clinical Isolates of Penicillin-Susceptible, Intermediate, and Resistant Pneumococci. Antimicrobial Agents and Chemotherapy, 46, 1273-1280. http://dx.doi.org/10.1128/AAC.46.5.1273-1280.2002
[2]	Kaniwa, K., Arai, M.A., Li, X. and Ishibashi, M. (2007) Synthesis, Determination of Stereochemistry, and Evaluation of New Bisindole Alkaloids from the Myxomycete Arcyriaferruginea: An Approach for Wnt Signal Inhibitor. Bioorganic & Medicinal Chemistry Letters, 17, 4254-4257. http://dx.doi.org/10.1016/j.bmcl.2007.05.033
[3]	Mingxing Teng, M. (2014) Total Synthesis of the Monoterpenoid Indole Alkaloid (±)-Aspidophylline A. Angewandte Chemie International Edition, 53, 1814-1817.
[4]	Pilar, M.F., Pedro, M. and Juan, A.B. (2001) Synthesis of the Indole Alkaloids Meridianins from the Tunicate Aplidium Meridianum. Tetrahedron, 57, 2355-2363. http://dx.doi.org/10.1016/S0040-4020(01)00102-8
[5]	Sharma, A. and Pathak, D.M. (2013) The Synthesis and Antimicrobial Activity of Indole Thiacarbamide Derivatives. International Journal of Scientific & Engineering Research, 4, 203-206.
[6]	Chavan Rajashree, S. and More Harinath, N. (2011) Synthesis, Characterization and Evaluation of Analgesic and Anti- Inflammatory Activities of Some Novel 2-(4,5-Dihydro-1H-pyrazol-3-yl)-3-phenyl-1H-indole. Journal of Pharmacy Research, 4, 1575-1578.
[7]	Kawasaki, I., Katsuma, H., Nakayama, Y., Yamashita, M.Y. and Ohta, S. (1998) Total Synthesis of Topsentin, Antiviral and Antitumor Bis(indolyl)imidazole. Heterocycles, 48, 1887-1901. http://dx.doi.org/10.3987/COM-98-8225
[8]	Kawasaki, I., Yamashita, M.Y. and Ohta, S. (1996) Total Synthesis of Nortopsentins A-D, Marine Alkaloids. Chemical and Pharmaceutical Bulletin, 44, 1831-1839. http://dx.doi.org/10.1248/cpb.44.1831
[9]	Sun, H.H. and Sakemi, J. (1991) A Brominated (Aminoimidazolinyl)indole from the Sponge Discodermia Polydiscus. The Journal of Organic Chemistry, 56, 4307-4308. http://dx.doi.org/10.1021/jo00013a045
[10]	Raju, R., Gromyko, O., Fedorenko, V., Luzhetskyy, A. and Müler, R. (2012) Pimprinols A-C, from the Terrestrial Actinomycete, Streptomyces sp. Tetrahedron Letters, 53, 3009-3011. http://dx.doi.org/10.1016/j.tetlet.2012.03.134
[11]	Fresneda, P.M., Castaneda, M., Blug, M. and Molina, P. (2007) Iminophosphorane-Based Preparation of 2,5-Disub- stituted Oxazole Derivatives: Synthesis of the Marine Aalkaloid Almazole C. Synlett, 2, 324-326. http://dx.doi.org/10.1055/s-2007-967995
[12]	Aaron, M.S., Richard, A.L. and David, C.R. (2007) Bacillamides from a Hypersaline Microbial Mat Bacterium. Journal of Natural Products, 70, 1793-1795. http://dx.doi.org/10.1021/np070126a
[13]	Gao, X., Chooi, Y.-H., Ames, B.D., Wang, P., Walsh, C.T. and Tang,Y. (2011) Fungal Indole Alkaloid Biosynthesis: Genetic and Biochemical Investigation of the Tryptoquialanine Pathway in Penicillium aethiopicum. Journal of the American Chemical Society, 133, 2729-2741. http://dx.doi.org/10.1021/ja1101085
[14]	Mohamed, A.R. and Mahmound, E.S. (2007) Synthesis and Antitumor Activity of Indolylpyrimidines: Marine Natural Product Meridianin D Analogues. Bioorganic & Medicinal Chemistry Letters, 15, 1206-1217. http://dx.doi.org/10.1016/j.bmc.2006.11.023
[15]	Sofy, A.R., Hmed, A.A., Sharaf, A.M. and El-Dougdoug, K.A. (2014) Structural Changes of Pathogenic Multiple Drug Resistance Bacteria Treated With T. Vulgaris Aqueous Extract. Nature and Science, 12, 83-88.
[16]	Caldeira, E.M., Osório, A., Oberosler, E.L., Vaitsman, D.S., Alviano, D.S. and Nojima, M.D.G. (2013) Antimicrobial and Fluoride Release Capacity of Orthodontic Bonding Materials. Journal of Applied Oral Science, 21, 327-334. http://dx.doi.org/10.1590/1678-775720130010
[17]	Kaya, E.G., Ozbilge, H. and Albayrak, S. (2009) Determination of the Effect of Gentamicin against Staphlococcus aureus by Using Microbroth Kinetic System. ANKEM Dergisi, 23,110-114.
[18]	March, S.J. (2000) Advanced Organic Chemistry: Reactions, Mechanisms and Structure. 5th Edition, John Wiley and Sons, New York, 1824.
[19]	Attaryan, O., Antanosyan, S., Panosyan, G., Asratyan, G. and Matsoyan, S. (2006) Vilsmeier Formyatiom of 3,5-Di-methylpyrazoles. Russian Journal of General Chemistry, 76, 1817-1819. http://dx.doi.org/10.1134/S1070363206110260
[20]	El-Nakkady, S.S., Hanna, M.M., Roaiah, H.M. and Ghannam, I.A. (2012) Synthesis, Molecular Docking Study and Antitumor Activity of Novel 2-Phenylindole Derivatives. European Journal of Medicinal Chemistry, 47, 387-398. http://dx.doi.org/10.1016/j.ejmech.2011.11.007
[21]	Saundane, A.R., Katkar, V.T. and Vaijinath, V. (2013) Synthesis, Antimicrobial, and Antioxidant Activities of N-[(5'- Substitut-ed-2'-phenyl-1H-indol-3-yl)methylene]-5H-dibenzo[b,f]azepine-5-carbohydrazide Derivatives. Journal of Chemistry, 2013, 1- 9. http://dx.doi.org/10.1155/2013/530135
[22]	Mahmouda, M.R., El-Ziatya, A.K., Abu El-Azma, F.S.M., Ismail, M.F. and Shibab, S.A. (2013) Utility of Cyano-N- (2-oxo-1,2-dihydroindol-3-ylidene)acetohydrazide in the Synthesis of Novel Heterocycles. Journal of Chemical Research, 37, 80-85. http://dx.doi.org/10.3184/174751912X13567100793191
[23]	Mohareb, R.M., El-Arab, E.E. and El-Sharkawy, K.A. (2009) The Reaction of Cyanoacetic Acid Hydrazide with 2-Acetylfuran: Synthesis of Coumarin, Pyridine, Thiophene and Tthiazole Derivatives with Potential Antimicrobial Activities. Scientia Pharmaceutica, 77; 355-366. http://dx.doi.org/10.3797/scipharm.0901-20
[24]	Darwish, E.S., Abdel Fattah, A.M., Attaby, F.A. and Al-Shayea, O.N. (2014) Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, Pyridone, Pyrazole, Chromene, Hydrazone Derivatives Bearing a Biologically Active Sulfonamide Moiety. International Journal of Molecular Sciences, 15, 1237-1254. http://dx.doi.org/10.3390/ijms15011237
[25]	Volmajer, J., Toplak, R., Leban, I. and Le Marechal, A.M. (2005) Synthesis of New Iminocoumarins and Their Transformations into N-Chloro and Hydrazono Compounds. Tetrahedron, 61, 7012-7021. http://dx.doi.org/10.1016/j.tet.2005.05.020
[26]	Alafeefy, A.M., Alqasoumi, S.I., Ashour, A.E., Masand, V., Al-Jaber, N.A., Hadda, T.B. and Mohamed, M.A. (2012) Quinazoline-Tyrphostin as a New Class of Antitumor Agents, Mo-lecular Properties Prediction, Synthesis and Biological Testing. European Journal of Medicinal Chemistry, 53, 133-140. http://dx.doi.org/10.1016/j.ejmech.2012.03.044
[27]	El-Gaml, K.M. (2015) Synthesis and Antimicrobial Evaluation of New Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyanoquinolin-2-yl)acetamide. American Journal of Organic Chemistry, 5, 1- 9.
[28]	Ravibabu, V., Janardhan, B., Rajitha, G. and Rajitha, B. (2013) Efficient One-Pot Three-Component Synthesis of Thiazolylpyrazole Derivatives under Conventional Method. Der Chemica Sinica, 4, 79-83.
[29]	Dilli Varaprasad, E., Mastan, M. and Sobha Rani, T. (2012) Synthesis and Evaluation of Analgesic Activity of Novel Series of Indole Derivatives Linked to Isoxazole Moiety. Der Pharmacia Lettre, 4, 1431-1437.
[30]	El-Nakkady, S., Abbas, S., Roaiah, H. and Ali, I. (2012) Synthesis, Antitumor and Anti-Inflammatory Ac-tivities of 2- Thienyl-3-Substitued Indole Derivatives. Global Journal of Pharmacology, 6, 166-177.
[31]	Chen, Z.-H., Zheng, C.-J., Sun, L.-P. and Piao, H.-R. (2010) Synthesis of New Chalcone Derivatives Containing Rhodanine-3-Acetic Acid Moiety with Potential Anti-Bacterial Activity. European Journal of Medicinal Chemistry, 45, 5739-5743. http://dx.doi.org/10.1016/j.ejmech.2010.09.031
[32]	Chaudhari, S.A., Sandeep, R., Patil, S.R., Patil, V.M., Patil, S.V., Jachak, M.N. and Desai, A. (2015) Synthesis of Pyrano[2,3-d]pyridine, Pyrazolo[3,4-b]pyridine Derivatives by Microwave Irradiation and Study of Their Insecticidal Activity. Journal of Chemical and Pharmaceutical Research, 9,476-482.
[33]	Shabaan, M., Taher, A.T. and Osma, E.O. (2011) Synthesis of Novel 3,4-Dihydroquinoxalin-2(1H)-one De-rivatives. European Journal of Chemistry, 2, 365-371. http://dx.doi.org/10.5155/eurjchem.2.3.365-371.289
[34]	Abdelhafez, O.M., Amin, K.M., Batran, R.Z., Maher, T.J., Somaia, A., Nada, S.A. and Sethumadhavan, S. (2010) Synthesis, Anticoagulant and PIVKA-II Induced by New 4-Hydroxycoumarin Derivatives. Bioorganic & Medicinal Chemistry, 18, 3371-3378. http://dx.doi.org/10.1016/j.bmc.2010.04.009