INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES

Begüm Evranos Aksöz; Fatma Kaynak Kaynak Onurdağ; Erkan Aksöz; Selda Özgen

doi:10.33483/jfpau.870815

Research Article

BAZI 4,5-DİHİDRO-1H-PİRAZOL VE ŞALKON TÜREVLERİNİN ANTİMİKROBİYAL VE ANTİTÜBERKÜLER ETKİLERİ ÜZERİNE ARAŞTIRMALAR

Year 2021, Volume: 45 Issue: 2, 227 - 237, 31.05.2021

Begüm Evranos Aksöz , Fatma Kaynak Kaynak Onurdağ , Erkan Aksöz , Selda Özgen

https://doi.org/10.33483/jfpau.870815

Abstract

Amaç: Bu çalışmada öncelikle şalkonlar ve bu şalkon türevlerinin hidrazitler ile reaksiyonu sonucu halka kapanması ile oluşan 4,5-dihidro-1H-pirazol yapısındaki bileşikler sentez edilmiş ve sentezlenen tüm bileşiklerin antimikrobiyal ve antitüberküler etkileri araştırılmıştır.

Gereç ve Yöntem: Benzaldehit ve asetofenon türevlerinin alkali ortamda metanol içindeki reaksiyonuyla elde edilen şalkonların, hidrazit türevleri ile etanol içindeki reaksiyonu sonucu 4,5-dihidro-1H-pirazol türevleri elde edilmiştir. Sentezlenen bu bileşiklerin antimikrobiyal etkileri mikrodilüsyon yöntemiyle, antitüberküler etkileri ise mikroplaka alamar mavisi deneyi ile saptanmıştır.

Sonuç ve Tartışma: Comparing E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pseudomonas aeruginosa izolat (gentamisine dirençli) ve Candida albicans’a karşı 4,5-dihidro-1H-pirazol yapısındaki bileşiklerin şalkonlardan daha etkili olduğu bulunmuştur. Staphylococcus aureus’a karşı ise şalkonlar 4,5-dihidro-1H-pirazol türevlerinden daha etkili bulunmuştur. Staphylococcus aureus izolat (MRSA) ve Mycobacterium tuberculosis’e karşı hem şalkonlar hem de 4,5-dihidro-1H-pirazol türevleri aynı etkiyi göstermiştir. B21 bileşiği Candida krusei üzerinde flukonazolle aynı etkiyi göstermiştir. B20 bileşiği ise Candida krusei üzerine flukonazolden daha etkili bulunmuştur.

Keywords

Antimikrobiyal etki, antitüberküler etki, 4.5-dihidro-1H-pirazol, şalkon

References

KAYNAKLAR 1. Tsega, A., Mekonnen, F. (2019). Prevalence, risk factors and antifungal susceptibility pattern of Candida species among pregnant women at Debre Markos Referral Hospital, Northwest Ethiopia. BMC Pregnancy and Childbirth, 19, 527-534.
2. Vanani, A.R., Mahdavinia, M., Kalantari, H., Khoshnood, S., Shirani, M. (2019). Antifungal effect of the effect of Securigera securidaca L. vaginal gel on Candida species. Current Medical Mycology, 5(3), 31-35.
3. Oyewole, O.A., Okoliegbe, I.N., Alkhalil, S., Isah, P. (2013). Prevalence of vaginal candidiasis among pregnant women attending Federal University of Technology, Minna, Nigeria, Bosso Clinic. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 4(1), 113-120.
4. Samaranayake, Y.H., Samaranayake, L.P. (1994). Candida krusei: biology, epidemiology, pathogenicity and clinical manifestations of an emerging pathogen. Journal of Medical Microbiology, 41, 295-310.
5. Nobile, C.J., Johnson, A.D. (2015). Candida albicans biofilms and human disease. Annual Review of Microbiology, 69, 71-92.
6. Kumar, K.A., Jayaroopa, P. (2013). Pyrazoles: synthetic strategies and their pharmaceutical applications-an overview. International Journal of PharmTech Research, 5(4), 1473-1486.
7. Naim, M.J., Alam, O., Nawaz, F., Alam, J., Alam, P. (2016). Current status of pyrazole and its biological activities. Journal of Pharmacy and BioAllied Sciences, 8(1), 2-17.
8. Kumar, S., Bawa, S., Drabu, S., Kumar, R., Gupta, H. (2009). Biological activities of pyrazoline derivatives -a recent development. Recent Patents on Anti-Infective Drug Discovery, 4(3), 154-163.
9. Karrouchi, K., Radi, S., Ramli, Y., Taoufik, J., Mabkhot, Y.N., Al-aizari, F.A., Ansar, M. (2018). Synthesis and pharmacological activities of pyrazole derivatives: a review. Molecules, 23, 134-218.
10. Evranos-Aksoz, B., Ucar, G., Tas, S.T., Aksoz, E., Yelekci, K., Erikci, A., Sara, Y., Iskit, A.B. (2017). New human monoamine oxidase A inhibitors with potential antidepressant activity: design, synthesis, biological screening and evaluation of pharmacological activity. Combinatorial Chemistry & High Throughput Screening, 20(6), 461-473.
11. Gomes, M.N., Muratov, E.N., Pereira, M., Peixoto, J.C., Rosseto, L.P., Cravo, P.V.L., Andrade, C. H., Neves, B. J. (2017). Chalcone derivatives: promising starting points for drug design. Molecules, 22(8), 1210.
12. Evranos Aksöz, B., Ertan, R. (2011). Chemical and structural properties of chalcones I. FABAD Journal of Pharmaceutical Sciences, 36, 223-242. 13. Zhuang, C., Zhang, W., Sheng, C., Zhang, W., Xing, C., Miao, Z. (2017). Chalcone: a privileged structure in medicinal chemistry. Chemical Reviews, 117(12), 7762-7810. 14. Sahu, N.K., Balbhadra, S.S., Choudhary, J., Kohli, D.V. (2012). Exploring pharmacological significance of chalcone scaffold: a review. Current Medicinal Chemistry, 19, 209-225.
15. Lin, Y.M., Zhou, Y., Flavın, M.T., Zhou, L.M., Nıe, W., Chen, F.C. (2002). Chalcones and flavonoids as anti-tuberculosis agents. Bioorganic and Medicinal Chemistry, 10, 2795-2802.
16. Jayasinghe, L., Balasooriya, B.A., Padmini, W.C., Hara, N., Fujimoto, Y. (2004). Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis. Phytochemistry, 65, 1287-1290.
17. Svetaz, L., Tapia, A., López, S.N., Furlán, R.L., Petenatti, E., Pioli, R., Schmeda-Hirschmann, G., Zacchino, S.A. (2004). Antifungal chalcones and new caffeic acid esters from Zuccagnia punctata acting against soybean infecting fungi. Journal of Agricultural Food Chemistry, 52, 3297-3330.
18. Özdemir, A., Turan-Zitouni, G., Kaplancıklı, Z.A., Revial, G., Demirci, F., İşcan, G. (2010). Preparation of some pyrazoline derivatives and evaluation of their antifungal activities. Journal of Enzyme Inhibition and Medicinal Chemistry, 25(4), 565-571.
19. Jimenez, C.M., Sampietro, D.A., Sgariglia, M.A., Soberón, J.R., Vattuone, M.A. (2014). Isolation, identification and usefulness of antifungal compounds from Zuccagnia punctata for control of toxigenic ear rot pathogens. Natural Products Communications, 9, 1461-1464.
20. Koudokpon, H., Armstrong, N., Dougnon, T.V., Fah, L., Hounsa, E., Bankolé, H.S., Loko, F., Chabrière, E., Rolain, J.M. (2018). Antibacterial activity of chalcone and dihydrochalcone compounds from Uvaria chamae roots against multidrug-resistant bacteria. BioMed Research International, 2018, 1453173.
21. Xu, M., Wu, P., Shen, F., Ji, J., Rakesh, K.P. Chalcone derivatives and their antibacterial activities: Current development. (2019). Bioorganic Chemistry, 91, 103133.
22. Ni, L., Meng, C.Q., Sikorski, J.A. (2004). Recent advances in therapeutic chalcones. Expert Opinion on Therapeutic Patents, 14(12), 1669-1691. 23. Evranos-Aksoz, B., Baysal, I., Yabanoglu-Ciftci, S., Djikic, T., Yelekci, K., Ucar, G., Ertan, R. (2015). Synthesis and screening of human Monoamine oxidase-A inhibitor effect of new 2-pyrazoline and hydrazone derivatives. Archive Der Pharmazie, 348, 743-756.
24. Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006a). Performance standards for antimicrobial susceptibility testing 6th ınformational supplement. CLSI M100-S16, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
25. Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006b). Reference method for broth dilution antifungal susceptibility testing of yeast approved standard, M27-A, clinical and laboratory standards ınstitute, 940 West Valley Road, Wayne, Pennsylvania, USA.
26. Franzblau, S.G., Witzig, R.S., McLaughlin, J.C., Torres, P., Madico, G., Hernandez, A., Degnan, M.T., Cook, M.B., Quenzer, V.K., Ferguson, R.M., Gilman, R.H. (1998). Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate alamar blue assay. Journal of Clinical Microbiology, 36, 362-366.
27. Lin, Y.M., Zhou, Y., Flavin, M.T., Zhou, L.M., Nie, W., Chen, F.C. (2002). Chalcones and flavonoids as anti-tuberculosis agents. Bioorganic and Medicinal Chemistry, 10, 2795-2802.

INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES

Year 2021, Volume: 45 Issue: 2, 227 - 237, 31.05.2021

Begüm Evranos Aksöz , Fatma Kaynak Kaynak Onurdağ , Erkan Aksöz , Selda Özgen

https://doi.org/10.33483/jfpau.870815

Abstract

Objective: In this study, first of all, chalcones and the compounds in the structure of 4,5-dihydro-1H-pyrazole, which are formed by ring closure as a result of the reaction of the chalcones with hydrazides were synthesized and the antimicrobial and antitubercular effects of all synthesized compounds were investigated.

Material and Method: 4,5-Dihydro-1H-pyrazole derivatives were obtained as a result of the reaction of chalcones acquired by the reaction of benzaldehyde and acetophenone derivatives in methanol in alkaline medium, with hydrazide derivatives in methanol. The antimicrobial effects of these synthesized compounds were determined by microdilution method and their antitubercular effects were determined by microplate alamar blue assay.

Result and Discussion: Compounds in the structure of 4,5-dihydro-1H-pyrazole were found to be more effective than chalcones against E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pseudomonas aeruginosa isolate (gentamicin resistant) and Candida albicans. Against the strain of Staphylococcus aureus, chalcones were found to be more effective than 4,5-dihydro-1H-pyrazole derivatives. Both chalcones and 4,5-dihydro-1H-pyrazole derivatives showed similar effect against Staphylococcus aureus isolate (MRSA) and Mycobacterium tuberculosis. Compound B21 had the same activity with fluconazole against Candida krusei. Compound B20 was found to be more effective than fluconazole against Candida krusei.

Keywords

Antimicrobial activity, antitubercular activity, chalcone, 4.5-dihydro-1H-pyrazole

References

KAYNAKLAR 1. Tsega, A., Mekonnen, F. (2019). Prevalence, risk factors and antifungal susceptibility pattern of Candida species among pregnant women at Debre Markos Referral Hospital, Northwest Ethiopia. BMC Pregnancy and Childbirth, 19, 527-534.
2. Vanani, A.R., Mahdavinia, M., Kalantari, H., Khoshnood, S., Shirani, M. (2019). Antifungal effect of the effect of Securigera securidaca L. vaginal gel on Candida species. Current Medical Mycology, 5(3), 31-35.
3. Oyewole, O.A., Okoliegbe, I.N., Alkhalil, S., Isah, P. (2013). Prevalence of vaginal candidiasis among pregnant women attending Federal University of Technology, Minna, Nigeria, Bosso Clinic. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 4(1), 113-120.
4. Samaranayake, Y.H., Samaranayake, L.P. (1994). Candida krusei: biology, epidemiology, pathogenicity and clinical manifestations of an emerging pathogen. Journal of Medical Microbiology, 41, 295-310.
5. Nobile, C.J., Johnson, A.D. (2015). Candida albicans biofilms and human disease. Annual Review of Microbiology, 69, 71-92.
6. Kumar, K.A., Jayaroopa, P. (2013). Pyrazoles: synthetic strategies and their pharmaceutical applications-an overview. International Journal of PharmTech Research, 5(4), 1473-1486.
7. Naim, M.J., Alam, O., Nawaz, F., Alam, J., Alam, P. (2016). Current status of pyrazole and its biological activities. Journal of Pharmacy and BioAllied Sciences, 8(1), 2-17.
8. Kumar, S., Bawa, S., Drabu, S., Kumar, R., Gupta, H. (2009). Biological activities of pyrazoline derivatives -a recent development. Recent Patents on Anti-Infective Drug Discovery, 4(3), 154-163.
9. Karrouchi, K., Radi, S., Ramli, Y., Taoufik, J., Mabkhot, Y.N., Al-aizari, F.A., Ansar, M. (2018). Synthesis and pharmacological activities of pyrazole derivatives: a review. Molecules, 23, 134-218.
10. Evranos-Aksoz, B., Ucar, G., Tas, S.T., Aksoz, E., Yelekci, K., Erikci, A., Sara, Y., Iskit, A.B. (2017). New human monoamine oxidase A inhibitors with potential antidepressant activity: design, synthesis, biological screening and evaluation of pharmacological activity. Combinatorial Chemistry & High Throughput Screening, 20(6), 461-473.
11. Gomes, M.N., Muratov, E.N., Pereira, M., Peixoto, J.C., Rosseto, L.P., Cravo, P.V.L., Andrade, C. H., Neves, B. J. (2017). Chalcone derivatives: promising starting points for drug design. Molecules, 22(8), 1210.
12. Evranos Aksöz, B., Ertan, R. (2011). Chemical and structural properties of chalcones I. FABAD Journal of Pharmaceutical Sciences, 36, 223-242. 13. Zhuang, C., Zhang, W., Sheng, C., Zhang, W., Xing, C., Miao, Z. (2017). Chalcone: a privileged structure in medicinal chemistry. Chemical Reviews, 117(12), 7762-7810. 14. Sahu, N.K., Balbhadra, S.S., Choudhary, J., Kohli, D.V. (2012). Exploring pharmacological significance of chalcone scaffold: a review. Current Medicinal Chemistry, 19, 209-225.
15. Lin, Y.M., Zhou, Y., Flavın, M.T., Zhou, L.M., Nıe, W., Chen, F.C. (2002). Chalcones and flavonoids as anti-tuberculosis agents. Bioorganic and Medicinal Chemistry, 10, 2795-2802.
16. Jayasinghe, L., Balasooriya, B.A., Padmini, W.C., Hara, N., Fujimoto, Y. (2004). Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis. Phytochemistry, 65, 1287-1290.
17. Svetaz, L., Tapia, A., López, S.N., Furlán, R.L., Petenatti, E., Pioli, R., Schmeda-Hirschmann, G., Zacchino, S.A. (2004). Antifungal chalcones and new caffeic acid esters from Zuccagnia punctata acting against soybean infecting fungi. Journal of Agricultural Food Chemistry, 52, 3297-3330.
18. Özdemir, A., Turan-Zitouni, G., Kaplancıklı, Z.A., Revial, G., Demirci, F., İşcan, G. (2010). Preparation of some pyrazoline derivatives and evaluation of their antifungal activities. Journal of Enzyme Inhibition and Medicinal Chemistry, 25(4), 565-571.
19. Jimenez, C.M., Sampietro, D.A., Sgariglia, M.A., Soberón, J.R., Vattuone, M.A. (2014). Isolation, identification and usefulness of antifungal compounds from Zuccagnia punctata for control of toxigenic ear rot pathogens. Natural Products Communications, 9, 1461-1464.
20. Koudokpon, H., Armstrong, N., Dougnon, T.V., Fah, L., Hounsa, E., Bankolé, H.S., Loko, F., Chabrière, E., Rolain, J.M. (2018). Antibacterial activity of chalcone and dihydrochalcone compounds from Uvaria chamae roots against multidrug-resistant bacteria. BioMed Research International, 2018, 1453173.
21. Xu, M., Wu, P., Shen, F., Ji, J., Rakesh, K.P. Chalcone derivatives and their antibacterial activities: Current development. (2019). Bioorganic Chemistry, 91, 103133.
22. Ni, L., Meng, C.Q., Sikorski, J.A. (2004). Recent advances in therapeutic chalcones. Expert Opinion on Therapeutic Patents, 14(12), 1669-1691. 23. Evranos-Aksoz, B., Baysal, I., Yabanoglu-Ciftci, S., Djikic, T., Yelekci, K., Ucar, G., Ertan, R. (2015). Synthesis and screening of human Monoamine oxidase-A inhibitor effect of new 2-pyrazoline and hydrazone derivatives. Archive Der Pharmazie, 348, 743-756.
24. Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006a). Performance standards for antimicrobial susceptibility testing 6th ınformational supplement. CLSI M100-S16, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA.
25. Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). (2006b). Reference method for broth dilution antifungal susceptibility testing of yeast approved standard, M27-A, clinical and laboratory standards ınstitute, 940 West Valley Road, Wayne, Pennsylvania, USA.
26. Franzblau, S.G., Witzig, R.S., McLaughlin, J.C., Torres, P., Madico, G., Hernandez, A., Degnan, M.T., Cook, M.B., Quenzer, V.K., Ferguson, R.M., Gilman, R.H. (1998). Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate alamar blue assay. Journal of Clinical Microbiology, 36, 362-366.
27. Lin, Y.M., Zhou, Y., Flavin, M.T., Zhou, L.M., Nie, W., Chen, F.C. (2002). Chalcones and flavonoids as anti-tuberculosis agents. Bioorganic and Medicinal Chemistry, 10, 2795-2802.

There are 24 citations in total.

Details

Primary Language	English
Subjects	Pharmacology and Pharmaceutical Sciences
Journal Section	Research Article
Authors	Begüm Evranos Aksöz Fatma Kaynak Kaynak Onurdağ 0000-0002-8758-3864 Erkan Aksöz 0000-0001-9183-3638 Selda Özgen
Publication Date	May 31, 2021
Submission Date	January 30, 2021
Acceptance Date	March 5, 2021
Published in Issue	Year 2021 Volume: 45 Issue: 2

Cite

APA	Evranos Aksöz, B., Kaynak Onurdağ, F. K., Aksöz, E., Özgen, S. (2021). INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES. Journal of Faculty of Pharmacy of Ankara University, 45(2), 227-237. https://doi.org/10.33483/jfpau.870815
AMA	Evranos Aksöz B, Kaynak Onurdağ FK, Aksöz E, Özgen S. INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES. J. Fac. Pharm. Ankara. May 2021;45(2):227-237. doi:10.33483/jfpau.870815
Chicago	Evranos Aksöz, Begüm, Fatma Kaynak Kaynak Onurdağ, Erkan Aksöz, and Selda Özgen. “INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University 45, no. 2 (May 2021): 227-37. https://doi.org/10.33483/jfpau.870815.
EndNote	Evranos Aksöz B, Kaynak Onurdağ FK, Aksöz E, Özgen S (May 1, 2021) INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES. Journal of Faculty of Pharmacy of Ankara University 45 2 227–237.
IEEE	B. Evranos Aksöz, F. K. Kaynak Onurdağ, E. Aksöz, and S. Özgen, “INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES”, J. Fac. Pharm. Ankara, vol. 45, no. 2, pp. 227–237, 2021, doi: 10.33483/jfpau.870815.
ISNAD	Evranos Aksöz, Begüm et al. “INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University 45/2 (May 2021), 227-237. https://doi.org/10.33483/jfpau.870815.
JAMA	Evranos Aksöz B, Kaynak Onurdağ FK, Aksöz E, Özgen S. INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES. J. Fac. Pharm. Ankara. 2021;45:227–237.
MLA	Evranos Aksöz, Begüm et al. “INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University, vol. 45, no. 2, 2021, pp. 227-3, doi:10.33483/jfpau.870815.
Vancouver	Evranos Aksöz B, Kaynak Onurdağ FK, Aksöz E, Özgen S. INVESTIGATIONS ON ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITY OF SOME 4,5-DIHYDRO-1H-PYRAZOLE AND CHALCONE DERIVATIVES. J. Fac. Pharm. Ankara. 2021;45(2):227-3.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.