Microwave-Assisted Synthesis and Antimicrobial Activity of Some Novel Isatin Schiff Bases Linked to Nicotinic Acid via Certain Amino Acid Bridge

Hindawi Publishing Corporation Journal of Chemistry Volume 2015, Article ID 364841, 8 pages http://dx.doi.org/10.1155/2015/364841 Research Article Microwave-Assisted Synthesis and Antimicrobial Activity of Some Novel Isatin Schiff Bases Linked to Nicotinic Acid via Certain Amino Acid Bridge Ahmed M. Naglah,1,2 Hassan M. Awad,3 Mashooq A. Bhat,4 Mohamed A. Al-Omar,1 and Abd El-Galil E. Amr1,5 1 Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 2 Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt 3 Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries Division, National Research Centre, Dokki, Cairo 12622, Egypt 4 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 5 Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt Correspondence should be addressed to Ahmed M. Naglah; Received 1 October 2014; Revised 30 November 2014; Accepted 21 December 2014 Academic Editor: Rabah Boukherroub Copyright © 2015 Ahmed M. Naglah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The coupling reaction of nicotinic acid with certain L-amino acid methyl esters including valine, leucine, and phenylalanine was done by the use of acid chloride method. The products were reacted with hydrazine hydrate 99% to give the corresponding hydrazides that were reacted with indoline-2,3-dione (isatin) to get Schiff bases under the application of microwave irradiation technique. These novel compounds were characterized by means of their FT-IR, 1 H NMR, and mass spectral data. Additionally, the specific optical rotation and elemental analysis were measured. The in vitro antimicrobial activity of the synthesized compounds was evaluated by agar diffusion method. The compounds showed a strong antimicrobial inhibitory activity. Most of the test compounds possessed a broad spectrum of activities having MIC values ranging from 50 𝜇g/mL to 500 𝜇g/mL. 1. Introduction Nicotinic acid (pyridine-3-carboxylic acid), also known as niacin and vitamin B3, is found in various plants and animals; also, it has vital roles in such biological processes as production of energy [1]. Nicotinic acid derivatives and its isomers have antibacterial, antioxidant, anti-inflammatory, anticarcinogenic, and antitubercular activities [2], signal transduction, regulation of gene expression [3], and involvement in the synthetic pathway of lipids [4]. On the other hand, some of new heterocyclic and peptide derivatives have been studied with respect to antivirus [5], anti-inflammatory [6], enzymatic peptide [7], and antimicrobial activities [8, 9]. Also, there are several successful publications of microwaveassisted solid phase peptide synthesis of various unnatural biopolymers such as peptoids, pseudopeptides, small peptides [10], phosphopeptides [11], difficult peptides [12], 𝛽peptide libraries [13], and glycopeptides [14]. It is as well known that isatin is an endogenous compound identified in humans and that its biological properties include a range of actions in the brain; it offers protection against certain types of infections [15]. Isatin constitutes an important class of bioactive compounds exhibiting caspase inhibitor [16, 17], antiproliferative [18], and antibacterial activities [19]. Furthermore, novel inhibitors of mycobacterium tuberculosis, prepared from indoline-2,3-dione (isatin) derivatives by the use of microwave irradiation technique, have been reported [20]. Due to the importance of nicotinic acid derivatives, amino acids, peptides, and isatin as bioactive compounds and 2 in continuation of our previous works in heterocyclic and peptide chemistry [21–26], the aim of this study is to prepare novel antimicrobial compounds that have crucial importance in the way of overcoming the remarkable adaptability of the bacteria. 2. Experimental 2.1. Chemistry 2.1.1. General. The organic solvents and the chemicals used in this part were obtained from Sigma (USA) and Fluka (Switzerland) chemical companies and the used amino acids are of L-configuration. Microwave irradiations were carried out using a domestic microwave oven LG-MS-2044 W/OO, with frequency of 2450 MHz and operating at 420 watts of the total power. Infrared (IR) spectra were recorded as KBr disks using the Perkin Elmer FT-IR Spectrum BX Apparatus located at the Research Center, College of Pharmacy, King Saud University (Riyadh, Saudi Arabia). Melting points were determined in opened glass capillary tubes with an “Electrothermal” Digital Melting Point Apparatus (model: IA9100) and are uncorrected. Elemental microanalysis for carbon, hydrogen, and nitrogen was measured at the Microanalytical Unit, National Research Centre (Cairo, Egypt), and was found within the acceptable limits of the calculated values (±0.4%). Specific optical rotations were measured at the National Research Centre (Cairo, Egypt) with “A. KRUSS, OPTRONIC, P8000” polarimeter (Germany), in a 1 dm length for the observation tube, in methanol as a solvent. NMR spectra were scanned in DMSO-𝑑6 on a Bruker NMR spectrophotometer operating at 500 MHz for 1 H at the Research Center, College of Pharmacy, King Saud University (Riyadh, Saudi Arabia). Chemical shifts are expressed in 𝛿-values (ppm) relative to tetramethylsilane (TMS) as an internal standard. Coupling constants (𝐽) are expressed in Hz. D2 O was added to confirm the exchangeable protons. High resolution mass spectra were measured on a JEOL M Station JMS-700 system at the Research Center, College of Pharmacy, King Saud University (Riyadh, Saudi Arabia). Analytical thin layer chromatography (TLC) was performed on silica gel aluminum sheets, 60 F254 (E. Merck). 2.1.2. Synthesis of Esters (3a–c). These compounds were prepared by the reaction of acid chloride 1 with amino acid esters 2a–c according to the reported method [27]. 2.1.3. Synthesis of Hydrazide Derivatives (4a–c). Hydrazine hydrate 99% (0.8 mL, 16 mmol) was added to a methanolic solution (10 mL) of 3a–c (1 mmol). The reaction mixture was refluxed for 10 h, after which the solvent was evaporated under reduced pressure. The obtained residue was triturated with ether, filtered off, and crystallized to afford the corresponding hydrazides (4a–c). The physical properties and spectral data of compounds N-(1hydrazinyl-3-methyl-1-oxobutan-2-yl)nicotinamide (4a) and Journal of Chemistry N-(1-Hydrazinyl-1-oxo-3-phenylpropan-2-yl)nicotinamide (4c) were identical with those reported in [28]. N-(1-Hydrazinyl-4-methyl-1-oxopentan-2-yl)nicotinamide (4b). Yield (66%); m. p. 182–185∘ C; −[𝛼]25 D = −80 (𝑐 = 0.02, MeOH); IR (KBr) ]max /cm−1 3413–3276 (...truncated)