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STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS

Yıl 2021, Cilt: 45 Sayı: 2, 182 - 193, 31.05.2021

Gül Bayram Abdoul Nzeyımana Semra Utku Mahmut Ülger Gönül Aslan Erdoğan Berçın

https://doi.org/10.33483/jfpau.867768

Öz

Objective: Multidrug-resistant pathogenic bacteria, fungi, and Mycobacterium tuberculosis infections continue to be increasingly widespread worldwide. In organic chemistry, the tiya-Michael type addition is also significant reaction in the synthesis of bioactive compounds. In this study, the aim is to synthesize the series of new Michael type addition products 2-amino-3-[(2-nitro-1-phenylpropyl)thio]propanoic acid (IIa-IIg) and to investigate their in vitro, antibacterial, antifungal and antitubercular activity.
Material and Method: IIa-IIg derivatives were performed combining β-methyl-β-nitrostyrenes (Ia-Ig) with L-cysteine using Michael addition reaction and characterized by 1HNMR, FTIR, ESI-LC/MS and elemental analysis. Microdilution method and resazurin microtiter assay were used to determine antimicrobial activities.
Result and Discussion: Comparing the activities of the synthesized compounds, IIa, IId and IIe were found to have significant activity, with a MIC value of 1.95 µg/ml, against Mycobacterium tuberculosis H37Rv strain. All synthesized novel compounds displayed moderate activity against tested bacterial and fungi strains. Among the synthesized compounds, IIb exhibited the best antibacterial and antifungal activity, with MIC values of 31.25, 31.25 and 15.6 µg/ml, against B. subtilis, E. faecium and C. albicans, respectively. It was clear that some of the synthesized compounds exhibited antimycobacterial activity which could be a very good candidate for clinical uses.

Anahtar Kelimeler

Antibacterial activity antifungal activity antimycobacterial activity β-methyl-β-nitrostyrene Michael type addition

Destekleyen Kurum

Mersin University

Proje Numarası

2018-1-AP2-2782.

Teşekkür

This work was supported by the Mersin University Scientific Research Funds (Grant number 2018-1-AP2-2782).

Kaynakça

  • Gajdacs, M. (2019). The concept of an ideal antibiotic: implications for drug design. Molecules, 24, 1-16.
  • Gajdacs, M., Albericio, F. (2019). Antibiotic resistance: from the bench to patients. Antibiotics, 8, 1-4.
  • Laxminarayan, R., Duse, A., Wattal, C., Zaidi, A.K.M, Wertheim, H.F.L., Sumpradit, N.,Vieghe, E., Hara, G.L., Gould, I.M., Goossens, H., Greko, C., So, A.D., Bigdeli, M., Tomson, G., Woodhouse, W., Ombaka, E., Peralta, A.Q., Qamar, F.N., Mir, F., Kariuki, S., Bhutta, Z.A., Coates, A., Bergstrom, R., Wright, G.D., Brown, E.D., Cars, O. (2013). Antibiotic resistance-the need for global solutions. Lancet Infectious Disease, 13, 1057–1098.
  • World Health Organization Web Site. (2020). Retrieved January 14, 2021, from https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf
  • Nielsen, S. F., Boesen, T., Larsen, M., Schonning, K., Kromann, H. (2004). Antibacterial chalcones--bioisosteric replacement of the 4'-hydroxy group. Bioorganic & Medicinal Chemistry, 12, 3047-3054.
  • Narasimhan, B., Belsare, D., Pharande, D., Mourya, V., Dhake, A. (2004). Esters, amides and substituted derivatives of cinnamic acid: synthesis, antimicrobial activity and QSAR investigations. European Journal of Medicinal Chemistry, 39, 827-834.
  • Kaap, S., Quentin, I., Tamiru, D., Shaheen, M., Eger, K., Steinfelder, H.J. (2003). Structure activity analysis of the pro-apoptotic, antitumor effect of nitrostyrene adducts and related compounds. Biochemical Pharmacology, 65, 603-610.
  • Mikami, Y., Yazawa, K., Maeda, A., Uno, J., Kubo, A., Saito, N., Kawakami, N. (1991). Antifungal activity of SL-1, a beta-nitrostyrene type pigment and its synthetic congeners. Journal of Antibiotics (Tokyo), 44, 1454-1456.
  • Wang, W.Y., Wu, Y.C., Wu, C.C. (2006). Prevention of platelet glycoprotein IIb/IIIa activation by 3,4-methylenedioxy-β-nitrostyrene, a novel tyrosine kinase inhibitor. Molecular Pharmacology, 70, 1380-1389.
  • Milhazes, N., Calheiros, R., Marques, M.P., Garrido, J., Cordeiro, M.N., Rodrigues, C., Cordeiro, M.N.D.S., Rodrigues, C., Quinteira, S., Novais, C., Peixe, L., Borges, F. (2006). β-Nitrostyrene derivatives as potential antibacterial agents: a structure-property-activity relationship Study. Bioorganic & Medicinal Chemistry, 14, 4078-4088.
  • Hsieh, P.W., Chang, Y.T., Chuang, W.Y., Shih, H.C., Chiang, S.Z., Wu, C.C. (2010). The synthesis and biologic evaluation of anti-platelet and cytotoxic β-nitrostyrenes. Bioorganic & Medicinal Chemistry, 18, 7621-7627.
  • Cornell, H., Nguyen, T., Nicoletti, G., Jackson, N., Hügel, H. (2014). Comparisons of halogenated β-nitrostyrenes as antimicrobial agents. Applied Sciences, 4, 380-389.
  • Villar, J.A.F.P., Lima, F.T.D., Veber, C.L., Oliveira, A.R.M., Calgarotto, A.K., Marangoni, S., Silva, S.L. (2008). Synthesis and evaluation of nitrostyrene derivative compounds, new snake venom phospholipase A2 inhibitors. Toxicon, 51, 1467-1478.
  • Rahmani-Nezhad, S., Safavi, M., Pordeli M., Ardestani, S.K., Khosravani, L., Pourshojaei, Y., Emami, M. S., Foroumadi, A., Shafiee, A. (2014). Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents. European Journal of Medicinal Chemistry, 86, 562-569.
  • Gokce, M., Ozcelik, B., Bakır, G., Karaoğlu, T., Bercin, E., Noyanalpan, N. (2004). Antiviral and antimicrobial activities of new nitrobutane derivatives. Arzneimittel-Forschung, 54, 891-897.
  • Gokce, M., Utku, S., Bercin, E., Özcelik, B., Karaoglu, T., Noyanalpan, N. (2005). Synthesis and in vitro antimicrobial and cytotoxicity activities of 2-[(2-nitro-1-phenylalkyl) thio] benzoic acid derivatives. Turkish Journal of Chemistry, 29, 207-217.
  • Utku, S., Gokce, M., Ozcelik, B., Bercin, E. (2008). Evaluation of antimicrobial activity of 2-[(2-nitro-1-phenylalkyl)thiomethyl] benzimidazole derivatives. Turkish Journal of Pharmaceutical Sciences, 5, 107-116.
  • Shi, Y., Carroll, K.S. (2020). Activity-based sensing for site-specific proteomic analysis of aysteine oxidation. Accounts of Chemical Research, 53, 20-31.
  • Piste, P. (2013). Cysteine-master antioxidant. International Journal of Pharmaceutical, Chemical and Biological Sciences, 3, 143-149.
  • Sobhani, S., Rezazadeh, S. (2010). Michael addition reaction of thioacetic acid (AcSH) to conjugated alkenes under solvent- and catalyst-free conditions. Phosphorus, Sulfur, and Silicon and the Related Elements, 185, 2076-2084.
  • Pei, Q. L., Han, W. Y., Wu, Z. J., Zhang, X. M., & Yuan, W. C. (2013). Organocatalytic iastereo-and enantioselective sulfa-Michael addition to α, β-disubstituted nitroalkenes. Tetrahedron, 69(26), 5367-5373.
  • Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2008). Performance Standards for Antimicrobial Susceptibility Testing 18th Informational Supplement. CLSI M100-S18, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
  • Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast Approved Standard, M27-A3, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
  • National Committee for Clinical Laboratory Standards. (2003). Susceptibility Testing of Mycobacteria, Nocardia, and Other Aerobic Actinomycetes: Approved Standard NCCLS Document M24-A. Wayne, Pennsylvania.
  • Nateche, F., Martin, A., Baraka, S., Palomino, J.C., Khaled, S., Portaels, F. (2006). Application of the resazurin microtitre assay for detection of multidrug resistance in Mycobacterium tuberculosis in Algiers. Journal of Medical Microbiology, 55, 857-860.
  • Pettit, R.K., Pettit, G.R., Hamel, E. Hamel, Hogan, F., Moser, B.R., Wolf, S., Pon, S., Chapuis, J.C., Schmidt, J.M. (2009). E-combretastatin and E-resveratrol structural modifications: Antimicrobial and cancer cell growth inhibitory β-E-nitrostyrenes. Bioorganic & Medicinal Chemistry, 17, 6606-6612.

BAZI MICHAEL TİPİ KATIM ÜRÜNLERİNİN SENTEZ ÇALIŞMASI VE ANTİMİKROBİYAL AKTİVİTELERİ

Yıl 2021, Cilt: 45 Sayı: 2, 182 - 193, 31.05.2021

Gül Bayram Abdoul Nzeyımana Semra Utku Mahmut Ülger Gönül Aslan Erdoğan Berçın

https://doi.org/10.33483/jfpau.867768

Öz

Amaç: Çoklu ilaca dirençli patojenik bakteri, mantar ve Mycobacterium tuberculosis enfeksiyonları dünya çapında giderek yaygınlaşmaya devam etmektedir. Organik kimyada, tiya-Michael tipi katım ayrıca biyoaktif bileşiklerin sentezinde önemli bir reaksiyondur. Bu çalışmada, 2-amino-3-[(2-nitro-1-fenilpropil)tiyo]propanoik asit Michael tip yeni katım ürünlerinin (IIa-IIg) sentezi ve antibakteriyel, antifungal ve antitüberküler aktivitelerinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: L-sistein ile β-metil-β-nitrostirenlerdenin (Ia-Ig) Michael katım reaksiyonu kullanılarak IIa-IIg türevleri sentezlenmiş ve yapıları 1HNMR, FTIR, ESI-LC/MS ve elemental analiz ile karakterize edilmiştir. Mikrodilüsyon yöntemi ve resazurin mikrotitre deneyi antimikrobiyal aktivitelerinin belirlenmesinde kullanılmıştır.
Sonuç ve Tartışma: Sentezlenen bileşiklerin aktiviteleri karşılaştırıldığında, IIa, IId ve IIe Mycobacterium tuberculosis H37Rv suşuna karşı, 1.95 µg/ml’lik MIC değeri ile dikkat çekici aktiviteye sahip olarak bulunmuştur. Yeni sentezlenen bileşiklerin hepsi test edilen bakteri ve mantar suşlarına karşı orta derecede aktivite göstermişlerdir. Sentezlenen bileşikler arasında, IIb, B. subtilis, E. faecium ve C. albicans'a karşı sırasıyla 31.25, 31.25 ve 15.6 µg/ml MIC değerleri ile en iyi antibakteryel ve antifungal aktivite sergilemiştir Sentezlenen bazı bileşikler gösterdikleri antimikobakteriyel aktiviteden dolayı klinik kullanım için iyi bir aday olacakları açıktır.

Anahtar Kelimeler

Antibakteriyel aktivite antifungal aktivite antimikobakteriyel etki β-metil-β-nitrostiren Michael tip katılım

Proje Numarası

2018-1-AP2-2782.

Kaynakça

  • Gajdacs, M. (2019). The concept of an ideal antibiotic: implications for drug design. Molecules, 24, 1-16.
  • Gajdacs, M., Albericio, F. (2019). Antibiotic resistance: from the bench to patients. Antibiotics, 8, 1-4.
  • Laxminarayan, R., Duse, A., Wattal, C., Zaidi, A.K.M, Wertheim, H.F.L., Sumpradit, N.,Vieghe, E., Hara, G.L., Gould, I.M., Goossens, H., Greko, C., So, A.D., Bigdeli, M., Tomson, G., Woodhouse, W., Ombaka, E., Peralta, A.Q., Qamar, F.N., Mir, F., Kariuki, S., Bhutta, Z.A., Coates, A., Bergstrom, R., Wright, G.D., Brown, E.D., Cars, O. (2013). Antibiotic resistance-the need for global solutions. Lancet Infectious Disease, 13, 1057–1098.
  • World Health Organization Web Site. (2020). Retrieved January 14, 2021, from https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf
  • Nielsen, S. F., Boesen, T., Larsen, M., Schonning, K., Kromann, H. (2004). Antibacterial chalcones--bioisosteric replacement of the 4'-hydroxy group. Bioorganic & Medicinal Chemistry, 12, 3047-3054.
  • Narasimhan, B., Belsare, D., Pharande, D., Mourya, V., Dhake, A. (2004). Esters, amides and substituted derivatives of cinnamic acid: synthesis, antimicrobial activity and QSAR investigations. European Journal of Medicinal Chemistry, 39, 827-834.
  • Kaap, S., Quentin, I., Tamiru, D., Shaheen, M., Eger, K., Steinfelder, H.J. (2003). Structure activity analysis of the pro-apoptotic, antitumor effect of nitrostyrene adducts and related compounds. Biochemical Pharmacology, 65, 603-610.
  • Mikami, Y., Yazawa, K., Maeda, A., Uno, J., Kubo, A., Saito, N., Kawakami, N. (1991). Antifungal activity of SL-1, a beta-nitrostyrene type pigment and its synthetic congeners. Journal of Antibiotics (Tokyo), 44, 1454-1456.
  • Wang, W.Y., Wu, Y.C., Wu, C.C. (2006). Prevention of platelet glycoprotein IIb/IIIa activation by 3,4-methylenedioxy-β-nitrostyrene, a novel tyrosine kinase inhibitor. Molecular Pharmacology, 70, 1380-1389.
  • Milhazes, N., Calheiros, R., Marques, M.P., Garrido, J., Cordeiro, M.N., Rodrigues, C., Cordeiro, M.N.D.S., Rodrigues, C., Quinteira, S., Novais, C., Peixe, L., Borges, F. (2006). β-Nitrostyrene derivatives as potential antibacterial agents: a structure-property-activity relationship Study. Bioorganic & Medicinal Chemistry, 14, 4078-4088.
  • Hsieh, P.W., Chang, Y.T., Chuang, W.Y., Shih, H.C., Chiang, S.Z., Wu, C.C. (2010). The synthesis and biologic evaluation of anti-platelet and cytotoxic β-nitrostyrenes. Bioorganic & Medicinal Chemistry, 18, 7621-7627.
  • Cornell, H., Nguyen, T., Nicoletti, G., Jackson, N., Hügel, H. (2014). Comparisons of halogenated β-nitrostyrenes as antimicrobial agents. Applied Sciences, 4, 380-389.
  • Villar, J.A.F.P., Lima, F.T.D., Veber, C.L., Oliveira, A.R.M., Calgarotto, A.K., Marangoni, S., Silva, S.L. (2008). Synthesis and evaluation of nitrostyrene derivative compounds, new snake venom phospholipase A2 inhibitors. Toxicon, 51, 1467-1478.
  • Rahmani-Nezhad, S., Safavi, M., Pordeli M., Ardestani, S.K., Khosravani, L., Pourshojaei, Y., Emami, M. S., Foroumadi, A., Shafiee, A. (2014). Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents. European Journal of Medicinal Chemistry, 86, 562-569.
  • Gokce, M., Ozcelik, B., Bakır, G., Karaoğlu, T., Bercin, E., Noyanalpan, N. (2004). Antiviral and antimicrobial activities of new nitrobutane derivatives. Arzneimittel-Forschung, 54, 891-897.
  • Gokce, M., Utku, S., Bercin, E., Özcelik, B., Karaoglu, T., Noyanalpan, N. (2005). Synthesis and in vitro antimicrobial and cytotoxicity activities of 2-[(2-nitro-1-phenylalkyl) thio] benzoic acid derivatives. Turkish Journal of Chemistry, 29, 207-217.
  • Utku, S., Gokce, M., Ozcelik, B., Bercin, E. (2008). Evaluation of antimicrobial activity of 2-[(2-nitro-1-phenylalkyl)thiomethyl] benzimidazole derivatives. Turkish Journal of Pharmaceutical Sciences, 5, 107-116.
  • Shi, Y., Carroll, K.S. (2020). Activity-based sensing for site-specific proteomic analysis of aysteine oxidation. Accounts of Chemical Research, 53, 20-31.
  • Piste, P. (2013). Cysteine-master antioxidant. International Journal of Pharmaceutical, Chemical and Biological Sciences, 3, 143-149.
  • Sobhani, S., Rezazadeh, S. (2010). Michael addition reaction of thioacetic acid (AcSH) to conjugated alkenes under solvent- and catalyst-free conditions. Phosphorus, Sulfur, and Silicon and the Related Elements, 185, 2076-2084.
  • Pei, Q. L., Han, W. Y., Wu, Z. J., Zhang, X. M., & Yuan, W. C. (2013). Organocatalytic iastereo-and enantioselective sulfa-Michael addition to α, β-disubstituted nitroalkenes. Tetrahedron, 69(26), 5367-5373.
  • Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2008). Performance Standards for Antimicrobial Susceptibility Testing 18th Informational Supplement. CLSI M100-S18, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
  • Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast Approved Standard, M27-A3, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
  • National Committee for Clinical Laboratory Standards. (2003). Susceptibility Testing of Mycobacteria, Nocardia, and Other Aerobic Actinomycetes: Approved Standard NCCLS Document M24-A. Wayne, Pennsylvania.
  • Nateche, F., Martin, A., Baraka, S., Palomino, J.C., Khaled, S., Portaels, F. (2006). Application of the resazurin microtitre assay for detection of multidrug resistance in Mycobacterium tuberculosis in Algiers. Journal of Medical Microbiology, 55, 857-860.
  • Pettit, R.K., Pettit, G.R., Hamel, E. Hamel, Hogan, F., Moser, B.R., Wolf, S., Pon, S., Chapuis, J.C., Schmidt, J.M. (2009). E-combretastatin and E-resveratrol structural modifications: Antimicrobial and cancer cell growth inhibitory β-E-nitrostyrenes. Bioorganic & Medicinal Chemistry, 17, 6606-6612.
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Gül Bayram 0000-0002-4154-8596

Abdoul Nzeyımana Bu kişi benim 0000-0002-1887-510X

Semra Utku 0000-0003-3181-9134

Mahmut Ülger 0000-0001-6649-4195

Gönül Aslan 0000-0002-1221-7907

Erdoğan Berçın Bu kişi benim 0000-0002-7318-8361

Proje Numarası 2018-1-AP2-2782.
Yayımlanma Tarihi 31 Mayıs 2021
Gönderilme Tarihi 25 Ocak 2021
Kabul Tarihi 23 Şubat 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 45 Sayı: 2

Kaynak Göster

APA Bayram, G., Nzeyımana, A., Utku, S., Ülger, M., vd. (2021). STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS. Journal of Faculty of Pharmacy of Ankara University, 45(2), 182-193. https://doi.org/10.33483/jfpau.867768
AMA Bayram G, Nzeyımana A, Utku S, Ülger M, Aslan G, Berçın E. STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS. Ankara Ecz. Fak. Derg. Mayıs 2021;45(2):182-193. doi:10.33483/jfpau.867768
Chicago Bayram, Gül, Abdoul Nzeyımana, Semra Utku, Mahmut Ülger, Gönül Aslan, ve Erdoğan Berçın. “STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS”. Journal of Faculty of Pharmacy of Ankara University 45, sy. 2 (Mayıs 2021): 182-93. https://doi.org/10.33483/jfpau.867768.
EndNote Bayram G, Nzeyımana A, Utku S, Ülger M, Aslan G, Berçın E (01 Mayıs 2021) STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS. Journal of Faculty of Pharmacy of Ankara University 45 2 182–193.
IEEE G. Bayram, A. Nzeyımana, S. Utku, M. Ülger, G. Aslan, ve E. Berçın, “STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS”, Ankara Ecz. Fak. Derg., c. 45, sy. 2, ss. 182–193, 2021, doi: 10.33483/jfpau.867768.
ISNAD Bayram, Gül vd. “STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS”. Journal of Faculty of Pharmacy of Ankara University 45/2 (Mayıs 2021), 182-193. https://doi.org/10.33483/jfpau.867768.
JAMA Bayram G, Nzeyımana A, Utku S, Ülger M, Aslan G, Berçın E. STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS. Ankara Ecz. Fak. Derg. 2021;45:182–193.
MLA Bayram, Gül vd. “STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS”. Journal of Faculty of Pharmacy of Ankara University, c. 45, sy. 2, 2021, ss. 182-93, doi:10.33483/jfpau.867768.
Vancouver Bayram G, Nzeyımana A, Utku S, Ülger M, Aslan G, Berçın E. STUDY ON SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME MICHAEL-TYPE ADDITION COMPOUNDS. Ankara Ecz. Fak. Derg. 2021;45(2):182-93.
 Kapak Resmi İndir

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.