Author: Media Noori Abdullah1
1Chemistry Department, College of Science, Salahaddin University, Erbil, Iraq
Abstract: New candidates of N-phenylpyrazoline derivatives were designed combining the Indole moiety to explore its potential as antimicrobial and antioxidant activity. The starting material synthesis was achieved through One-pot three-component reaction; at that point, it was acylated and interacted with various substituted benzaldehydes to result in new chalcones that were later cyclized to N-phenylpyrazoline, through reaction with phenyl hydrazine. The structures of the synthesized compounds were reinforced by their spectral data. The final compounds were screened for antibacterial activity against resistant strains of Staphylococcus aureus and Escherichia coli microorganisms; as a result, it showed that the compounds with methoxy group at position meta and hydroxy at position ortho were the highly active derivatives. Meanwhile, the highly active compound with antifungal activity against C. Albicans, had nitro group at para position. During the evaluation of proton donating antioxidant activity, using DPPH radical scavenging assays method; it was exposed that, the derivatives with highly active antibacterial had the most antioxidant activity. In the final step, the molecular docking study exposed that the compound with highly active antibacterial and antioxidant activity was the most potent derivative. The resulting studies disclosed that the synthesized N-phenylpyrazoline derivatives displayed less specificity than the reference compounds.
Keywords: One Pot Reaction, Chalcone, N-Phenylpyrazoline, Antimicrobial, Dpph Scavenging Activity, Molecular Docking Study
Ahmad, M. R., Sastry, V. G., Bano, N., & Anwar, S. (2016). Synthesis of novel chalcone derivatives by conventional and microwave irradiation methods and their pharmacological activities. Arabian Journal of Chemistry, 9, S931-S935.
Aksöz, B. E., & Ertan, R. (2012). Spectral properties of chalcones II. Fabad J. Pharm. Sci, 37(4), 205-216.
Attarde, M., Vora, A., Varghese, A., & Kachwala, Y. (2014). Synthesis and evaluation of chalcone derivatives for its alpha amylase inhibitory activity. Organic Chemistry: An Indian Journal, 10, 192-204.
Biswal, S., Sahoo, U., Sethy, S., Kumar, H., & Banerjee, M. (2012). Indole: the molecule of diverse biological activities. Asian J. Pharm. Clin. Res, 5, 1-6.
Cong, H., Zhao, X., Castle, B. T., Pomeroy, E. J., Zhou, B., Lee, J., Wang, Y., Bian, T., Miao, Z., & Zhang, W. (2018). An Indole–Chalcone Inhibits Multidrug-Resistant Cancer Cell Growth by Targeting Microtubules. Molecular Pharmaceutics, 15, 3892-3900.
Dawood, D. H., Nossier, E. S., Ali, M. M. & Mahmoud, A. E. (2020). Synthesis and molecular docking study of new pyrazole derivatives as potent anti-breast cancer agents targeting VEGFR-2 kinase. Bioorganic Chemistry, 103916.
Devi, C. L., Rao, V. J., & Palaniappan, S. (2012). PANI-HBF4: a reusable polymer-based solid acid catalyst for three-component, one-pot synthesis of 3-substituted amino methyl indoles under solvent-free conditions. Synthetic Communications, 42, 1593-1603.
El-Sawy, E., Mandour, A., Mahmoud, K., Islam, I., & Abo-Salem, H. (2012). Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles. Acta Pharmaceutica, 62, 157-179.
Fishovitz, J., Hermoso, J. A., Chang, M., & Mobashery, S. (2014). Penicillin‐binding protein 2a of methicillin‐resistant Staphylococcus aureus. IUBMB Life, 66, 572-577.
Gaonkar, S. L. & Vignesh, U. (2017). Synthesis and pharmacological properties of chalcones: a review. Research on chemical intermediates, 43, 6043-6077.
Gomes, M. N., Muratov, E. N., Pereira, M., Peixoto, J. C., Rosseto, L. P., Cravo, P. V., Andrade, C. H., & Neves, B. J. (2017). Chalcone derivatives: promising starting points for drug design. Molecules, 22, 1210.
Grimster, N. P., Gauntlett, C., Godfrey, C. R., & Gaunt, M. J. (2005). Palladium‐Catalyzed Intermolecular Alkenylation of Indoles by Solvent‐Controlled Regioselective C H Functionalization. Angewandte Chemie International Edition, 44, 3125-3129.
Gupta, R., Gupta, N., & Jain, A. (2010). Improved synthesis of chalcones and pyrazolines under ultrasonic irradiation.
Hassan, S. A. (2019). Synthesis, Spectroscopic study, and biological activity of some New Heterocyclic compounds derived from Sulfadiazine. ZANCO Journal of Pure and Applied Sciences, 31, 92-109.
Ibrahim, M. N. (2007). Studies on Acetylation of Indoles. Journal of Chemistry, 4, 415-418.
Katritzky, A. R., Suzuki, K., Singh, S. K., & He, H.Y. (2003). Regiospecific C-acylation of pyrroles and indoles using N-acylbenzotriazoles. The Journal of organic chemistry, 68, 5720-5723.
Landage, V., Thube, D., & Karale, B. (2019). Synthesis, characterisation and antimicrobial screening of some new thiazolyl chromones and pyrazoles.
Lévai, A., & Jeko, J. (2000). Synthesis of carboxylic acid derivatives of 2-pyrazolines. Arkivoc, 1, 134-45.
Mathur, A., Singh, R., Yousuf, S., Bhardwaj, A., Verma, S. K., Babu, P., Gupta, V., Prasad, G. & Dua, V. (2011). Antifungal activity of some plant extracts against clinical pathogens. Advances in applied science Research, 2, 260-264.
Mowlana, M. Y. & Nasser, A. (2015). Synthesis and Molecular Docking studies of Heterocyclic Chalcone Derivatives as BRCA1 inhibitors. International Journal of Pharmaceutical Chemistry, 3, 196-200.
Ottoni, O., Neder, A. D. V., Dias, A. K., Cruz, R. P., & Aquino, L. B. (2001). Acylation of Indole under Friedel− Crafts Conditions an Improved Method To Obtain 3-Acylindoles Regioselectively. Organic Letters, 3, 1005-1007.
Özdemir, A., Altıntop, M. D., Turan-Zitouni, G., Çiftçi, G. A., Ertorun, İ., Alataş, Ö., & Kaplancıklı, Z. A. (2015). Synthesis and evaluation of new indole-based chalcones as potential antiinflammatory agents. European journal of medicinal chemistry, 89, 304-309.
Patel, H., Rajani, D., Sharma, M., & Bhatt, H. (2019). Synthesis, molecular docking and biological evaluation of mannich products based on thiophene nucleus using ionic liquid. Letters in Drug Design & Discovery, 16, 119-126.
Rahman, M. A., & Siddiqui, A. A. (2010). Pyrazoline derivatives: a worthy insight into the recent advances and potential pharmacological activities. Int J Pharm Sci Drug Res, 2, 165-175.
Robinson, M. W., Overmeyer, J. H., Young, A. M., Erhardt, P. W., & Maltese, W. A. (2012). Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death. Journal of medicinal chemistry, 55, 1940-1956.
Safaei-Ghomi, J., Bamoniri, A., & Soltanian-Telkabadi, M. (2006). A modified and convenient method for the preparation of N-phenylpyrazoline derivatives. Chemistry of Heterocyclic Compounds, 42, 892-896.
Sayed, M., Kamal El‐Dean, A. M., Ahmed, M., & Hassanien, R. (2018). Synthesis, Characterization, and Screening for Anti‐inflammatory and Antimicrobial Activity of Novel Indolyl Chalcone Derivatives. Journal of Heterocyclic Chemistry, 55, 1166-1175.
Singh, A. K., Prasad, R. K., & Singh, C. S. (2013). Synthesis, characterization and pharmacological evaluation of some novel 3-indole derivatives. Der Pharma Chemica, 5, 311-319.
Singh, T. P., & Singh, O. M. (2018). Recent progress in biological activities of indole and indole alkaloids. Mini Reviews in Medicinal Chemistry, 18, 9-25.
Subhashini, N. (2015). TT 1 and Shivaraj. Synthesis characterization and anti-bacterial activity of novel chalcone derivatives of indole, 38-45.
Tran, P. H., Tran, H. N., Hansen, P. E., Do, M. H. N., & Le, T. N. (2015). A simple, effective, green method for the regioselective 3-acylation of unprotected indoles. Molecules, 20, 19605-19619.
Zhuang, C., Zhang, W., Sheng, C., Zhang, W., Xing, C., & Miao, Z. (2017). Chalcone: a privileged structure in medicinal chemistry. Chemical reviews, 117, 7762-7810.