Heterocyclic Amides Derived from 2-Thiopheneacetic Acid: Synthesis, Characterization and Antimicrobial Activity Evaluation

Öz

The heterocyclic amide derivatives (I-IV) were synthesized from 2-thiophenacetic acid in two steps. In the first step, the intermediate acylation agent formed and isolated, then subjected to aminolysis and the corresponding amide derivatives were obtained. The structures of compounds obtained were characterized by FT-IR, 13C NMR, 1H NMR, spectroscopies and elemental analysis techniques. The antibacterial activities of these four compounds against Gram-negative bacteria, Gram-positive bacteria and fungi were investigated using the minimum inhibition concentration method. As a result, compounds (I and III) exhibited better good antibacterial activities against Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa compared to commercially standard antibacterial agent of amoxicillin.

Anahtar Kelimeler

• Acyl chloride,
• heterocyclic amides,
• antimicrobial activity,
• aminolysis,
• spectroscopic evaluation

2-Tiyofenasetik Asitten Türetilen Heterosiklik Amitler: Sentez, Karakterizasyon ve Antimikrobiyal Aktivitesinin Değerlendirilmesi

Öz

Heterosiklik amid türevleri (I-IV), iki aşamada 2-tiyofenasetik asitten sentezlendi. İlk aşamada, ara açilasyon ajanı oluşturuldu ve izole edildi, ardından aminolize tabi tutuldu ve karşılık gelen amid türevleri elde edildi. Elde edilen bileşiklerin yapıları FT-IR, 13C NMR, 1H NMR, spektroskopi ve element analiz teknikleri ile karakterize edildi. Bu dört bileşiğin Gram negatif bakterilere, Gram pozitif bakterilere ve mantarlara karşı antibakteriyel aktivitesi minimum inhibisyon konsantrasyon yöntemi kullanılarak araştırıldı. Sonuç olarak, bileşikler (I ve III), ticari olarak temin edilebilen amoksisilinin antibakteriyel standardına göre Staphylococcus aureus, Enterococcus faecalis ve Pseudomonas aeruginosa'ya karşı daha iyi antibakteriyel aktivite sergilediği gözlemlenmiştir.

Anahtar Kelimeler

• Asit klorür,
• heterosiklik amit,
• antimikrobiyal aktivite,
• aminoliz,
• spektroskopik değerlendirme

Kaynakça

1. [1]. Yasser, F.M., “Synthesis, Characterization and Antibacterial Activity of Novel Heterocycle, Coumacine, and Two of Its Derivatives”, Saudi Pharmaceutical Journal, 2018, 26: 870–875.
2. [2]. Pawar, N.S., Dalal, D.S., Shimpi, S.R., Mahulikar, P.P., “Studies of Antimicrobial Activity of N-alkyl and N-acyl 2-(4-thiazolyl)-1H-benzimidazoles”, European Journal of Pharmaceutical Sciences, 2004, 21: 115–118.
3. [3]. Al-Smadi, M.L., Mansour, R., Mahasneh, A., Khabour, O.F., Masadeh, M.M., Alzoubi, K.H., “Synthesis, Characterization, Antimicrobial Activity, and Genotoxicity Assessment of Two Heterocyclic Compounds Containing 1,2,3-Selena- or 1,2,3-Thiadiazole Rings”, Molecules, 2019, 24: 4082.
4. [4]. Desai, N.C., Pandya, D., Vaja, D., “Synthesis and Antimicrobial Activity of Some Heterocyclic Compounds Bearing Benzimidazole and Pyrazoline Motifs”, Medicinal Chemistry Research, 2018, 27: 52–60.
5. [5]. Padmavathi, V., Thriveni, P., Sudhakar Reddy, G., Deepti, D., “Synthesis and Antimicrobial Activity of Novel Sulfone-Linked Bis Heterocycles”, European Journal of Medicinal Chemistry, 2008, 43: 917–924.
6. [6]. Karcı, F., Sener, N., Yamac, M., Sener, I., Demircalı, A., “The Synthesis, Antimicrobial Activity and Absorption Characteristics of Some Novel Heterocyclic Disazo Dyes”, Dyes and Pigments, 2009, 80: 47–52.
7. [7]. Nasser, M.A.E.S, Mohamed, S.M., Ahmed, G.A., Alothman, O.Y., “Synthesis and Antimicrobial Activities of Some New Heterocyclic Compounds Based on 6-Chloropyridazine-3(2H)-thione”, Journal of Chemistry, 2013, 1–8.
8. [8]. Yildiz-Oren, I., Yalcin, I., Aki-Sener, E., Ucarturk, N., “Synthesis and Structure–Activity Relationships of New Antimicrobial Active Multisubstituted Benzazole Derivatives”, European Journal of Medicinal Chemistry, 2004, 39: 291–298.

9. [9]. Aytemir, M.D., “Synthesis of New Antimicrobial Agents; Amide Derivatives of Pyranones and Pyridinones”, Turkish Journal of Chemistry, 2003, 27: 445–452.
10. [10]. Baytas, S.N., Inceler, N., Orhan, D.D., Ozkan, S., “Synthesis, Characterization and Antioxidant and Antimicrobial Properties of New Ester and Amide Derivatives of Indole-2-Carboxylic Acid”, FABAD Journal of Pharmaceutical Sciences, 2011, 36: 53–61.
11. [11]. Perrelli, A., Goitre, L., Salzano, A.M., Moglia, A., Scaloni, A., Retta, S.F., “Biological Activities, Health Benefits, and Therapeutic Properties of Avenanthramides: From Skin Protection to Prevention and Treatment of Cerebrovascular Diseases”, Hindawi Oxidative Medicine and Cellular Longevity, 2018, 1–17.
12. [12]. Patil, M., Bendre, R., “Synthesis, Characterization and Antioxidant Potency of Naturally Occurring Phenolic Monoterpenoids Based Hydrazide Motifs”, Medicinal Chemistry, 2018, 8(7): 177–180.
13. [13]. Limban, C., Missir, A.V., Nuţă, D.C., Căproiu, M.T., Papacocea, M.T., “Synthesis of Some New 2-((4-chlorophenoxy)methyl)-N-(arylcarbamothioyl)benzamides as Potential Antifungal Agents”, Farmacia, 2016, 64(5): 775–779.
14. [14]. Kabara, J.J., Conley, A.J., Truant, J.P., “Relationship of Chemical Structure and Antimicrobial Activity of Alkyl Amides and Amines”, Antimicrobial Agents and Chemotheraoy, 1972, 2(6): 492–498.
15. [15]. Bayoumi, W.A., Elsayed, M.A., “Synthesis of New Phenylcarbamoylbenzoic Acid Derivatives and Evaluation of Their in Vitro Antioxidant Activity”, Medicinal Chemistry Research, 2012, 21(8): 1633–1640.
16. [16]. Jung, M.E., Abrecht, S., “Improved Synthesis of 3-Substituted 7-Methoxybenzofurans. Useful Intermediates for The Preparation of Morphine Analogs of Organic Chemistry”, The Journal of Organic Chemistry, 1988, 53(2): 423–425.
17. [17]. Mazik, M., Bläser, D., Boese, R., “Hydrogen-Bonding Motifs in The Crystals of Secondary Diamides with 2-amino-6-methyl- and 2,6-diaminopyridine Subunits”, Tetrahedron, 1999, 55(44): 12771–12782.
18. [18]. Kırca, B.K., Cakmak, S., Kutuk, H., Odabasoglu, M., Buyukgungor, O., “Synthesis and Characterization of 3-acetoxy-2-methyl-N-(phenyl)benzamide and 3-acetoxy-2-methyl-N-(4- methylphenyl)benzamide”, Journal of Molecular Structure, 2018, 1151: 191–197.
19. [19]. Demir, S., Cakmak, S., Dege, N., Kutuk, H., Odabasoglu, M., Kepekci, R.A., “A Novel 3-acetoxy-2-methyl-N-(4-methoxyphenyl)benzamide: Molecular Structural Describe, Antioxidant Activity with Use X-Ray Diffractions and DFT Calculations”, Journal of Molecular Structure, 2015, 1100: 582–591.
20. [20]. Schwalbe, R., Steele-moore, L., Goodwin, A., “Antimicrobial Susceptibility Testing Protocols”, 2007, 430.
21. [21]. Yakan, H., Cakmak, S., Kutuk, H., Yenigun, S., Ozen T., “Synthesis, Characterization, Antioxidant, and Antibacterial Activities of New 2, 3-dimethoxy and 3-acetoxy-2-methyl benzamides”, Research on Chemical Intermediates, 2020, 46: 2767–2787.
22. [22]. Ören, İ.Y., Şener, E.A., Ertaş, C., Arpaci, Ö.T., Yalçin, İ., Altanlar, N., “Synthesis and Microbiological activity of Some Substituted N-(2-hydroxy-4-nitrophenyl)benzamides, phenylacetamides as Possible Metabolites of Antimicrobial Active Benzoxazoles”, Turkish Journal of Chemistry, 2004, 28: 441–449.