Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds

Göknil Coşkun; Akın Aklamuz; Ufuk İnce; Mert Ülgen

doi:10.17776/csj.1105811

Research Article

Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds

Year 2022, , 384 - 390, 30.09.2022

Göknil Coşkun , Akın Aklamuz Ufuk İnce Mert Ülgen

https://doi.org/10.17776/csj.1105811

Cited By: 2

Abstract

Bacterial infection today occupies a tremendous place in world health. The infection diseases were kept under control after the development of penicillin and further studies were performed on the development of new antibacterial agents. However, to date, bacterial resistance caused a big failure in the treatment of infectious disease and therefore, development of new antibacterial agents became important for human health. In the present study, we have designed, synthesized and elucidated the structures of new hydrazide-hydrazone compounds and their hybrid amide derivatives. The structures of the compounds were elucidated with spectroscopic methods and their purity were proven by TLC, HPLC-MS analysis. The antibacterial and antifungal activity studies of the novel molecules were investigated on different strains. Among the synthesized compounds, AA3a and AA4a appeared to show promising antibacterial activity. None of the compounds showed significant antifungal activity on Candida albicans. The drug likeness properties and boiled-egg plot analysis were performed for all of the compounds. The novel molecules showed no violation on Lipinski’s rule of five and all the molecules showed good gastrointestinal absorption properties in the in silico studies.

Keywords

4-ASA, Hydrazide, Hydrazone, Amide, Antibacterial activity.

Supporting Institution

TUBITAK

Project Number

This study was granted by TUBITAK 2209-A 2021/1 1919B012100499

Thanks

References

[1] Zheng H., Li H., Deng H., Fang W., Huang X., Qiao J., Tong Y., Near İnfrared Light-Responsive And Drug-Loaded Black Phosphorus Nanosheets For Antibacterial Applications, Colloids Surf B Biointerfaces, 214 (2022) 112433.
[2] Theuretzbacher U., Resistance drives antibacterial drug development, Curr. Opin. Pharmacol, 11(5) (2011) 433-8.
[3] Kaplan Ö., Gökşen N. Biosynthesis of silver nanoparticles from Teucrioside and investigation of its antibacterial activity, Cumhuriyet Sci. J., 42 (1) (2021) 60-67.
[4] Aşan Özüsağlam M. , Tacer S. , Boulechfar S., Zellaguı A. An Investigation of the Bactericidal and Fungicidal Effects of Algerian Propolis Extracts and Essential Oils., Cumhuriyet Sci. J., 43 (1) (2022) 14-19.
[5] Akgül Ö., Akgünlü Ç., Biler H., Ateş A., Ermertcan Ş. Antimicrobial activity screening of a series of taurine derivatives, Cumhuriyet Science J, 42 (4) (2021) 781-788.
[6] Lister P.D., The role of pharmacodynamic research in the assessment and development of new antibacterial drugs, Biochem Pharmacol, 71(7) (2006) 1057-65.
[7] Boulebda H., Zinea Y., Khodjaa I.A., Mermer A., Demir A., Debache A., Synthesis and radical scavenging activity of new phenolic hydrazone/hydrazide derivatives: Experimental and theoretical studies, J. Mol. Struct., 1249 (2022) 131546.
[8] Komurcu S.G., Rollas S., Ulgen M., Gorrod J.W., Cevikbas A., Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism, Boll Chim. Farm., 134(7) (1995) 375-9.
[9] Ulgen M., Durgun B.B., Rollas S., Gorrod J.W., The in vitro hepatic microsomal metabolism of benzoic acid benzylidenehydrazide, Drug Metabol Drug Interact, 13(4) (1997) 285-94.
[10] P. Vijaya G., Sundaraselvan., Synthesis, characterization, PASS analysis and ADMET properties of oxazolone ring containing hydrazone derivatives, Materials Today: Proceedings, 48 (2022) 502–507.
[11] Chen J., Lu W., Chen H., Bian X., Yang G., A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants, Biol. Pharm. Bull, 42(2) (2019) 231-246.
[12] Yamada H., Kojo M., Nakahara T., Murakami K., Kakima T., Ichiba H., Yajima T., Fukushima T., Development of a fluorescent chelating ligand for scandium ion having a Schiff base moiety, Spectrochim. Acta A. Mol. Biomol. Spectrosc., 90 (2012) 72-7.
[13] Clinical and L.S. Institute, Performance standards for antimicrobial susceptibility testing, Clinical and Laboratory Standards Institute Wayne, PA. (2017).
[14] Wayne, P., Clinical and Laboratory Standards Institute: Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, CLSI Document M27-A3 and Supplement S., 3 (2008) 6-12.
[15] Shi L., Ge H.M., Tan S.H., Li H.Q., Song Y.C., Zhu H.L., Tan R.X., Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde, Eur. J. Med. Chem., 42 (4) (2007) 558-64.
[16] Rollas S., Küçükgüzel S.G., Biological activities of hydrazone derivatives, Molecules, 12(8) (2007) 1910-39.
[17] Küçükgüzel S.G., Mazi A., Sahin F., Oztürk S., Stables J., Synthesis and biological activities of diflunisal hydrazide-hydrazones, Eur. J. Med. Chem., 38 (11-12) (2003) 1005-13.
[18] Şenkardeş S., Kaushik-Basu N., Durmaz İ., Manvar D., Basu A., Atalay R., Küçükgüzel Ş.G., Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors, Eur. J. Med. Chem., 27(108) (2016) 301-308.
[19] Rollas S., Kucukguzel S.G., Hydrazone, amide, carbamate, macromolecular and other prodrugs of doxorubicin, Open Drug Delivery Journal, 2 (2008) 77-85.
[20] Küçükgüzel Ş.G., Koç D., Çıkla-Süzgün P., Özsavcı D., Bingöl-Özakpınar Ö., Mega-Tiber P., Orun O., Erzincan P., Sağ-Erdem S., Şahin F., Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells, Arch. Pharm. (Weinheim), 348(10) (2015) 730-42.
[21] Küçükgüzel S.G., Rollas S.. Synthesis, characterization of novel coupling products and 4-arylhydrazono-2-pyrazoline-5-ones as potential antimycobacterial agents, Farmaco, 57(7) (2002) 583-7.
[22] Han M.I., Guler G., Temel Y., Sadik K., Kucukguzel S.G., Synthesis and antibacterial activity of new hydrazide-hydrazones derived from Benzocaine, Marmara Pharm. J., 21(4) (2017) 961-966.
[23] Çıkla-Süzgün P., Küçükgüzel Ş.G., Recent Advances in Apoptosis: THE Role of Hydrazones, Mini Rev. Med. Chem., 19(17) (2019) 1427-1442.
[24] Şenkardeş S., Han M.İ., Kulabaş N., Abbak M., Çevik Ö., Küçükgüzel İ., Küçükgüzel Ş.G., Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors, Mol. Divers, 24(3) (2020) 673-689.
[25] Çıkla P., Özsavcı D., Bingöl-Özakpınar Ö., Şener A., Çevik Ö., Özbaş-Turan S., Akbuğa J., Şahin F., Küçükgüzel Ş.G., Synthesis, cytotoxicity, and pro-apoptosis activity of etodolac hydrazide derivatives as anticancer agents, Arch. Pharm. (Weinheim), 346(5) (2013) 367-79.
[26] Hamzacebi M.C., Rollas S., Kucukguzel, S.G., Kocyigit-Kaymakcioglu B., Synthesis and structure elucidation of hydrazones derived from N-(2,4-dimethylphenyl)-3-oxobutanamide, ARKIVOC (Gainesville, FL, United States), (12) (2008) 188-194.
[27] Kucukguzel S.G., Rollas S., Kucukguzel I., Kiraz M., Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones, Eur. J. Med. Chem., 34(12) (1999) 1093-1100.
[28] Koc H.C., Atlihan I., Mega-TIber P., Orun O., Kucukguzel S.G., Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents, J. Res. Pharm., 26(1) (2022) 1-12.
[29] Cikla P., Kucukguzel G., Kucukguzel I., Rollas S., De Clercq E., Pannecouque C., Andrei G., Snoeck R., Sahin F., Bayrak O.F., Synthesis and evaluation of antiviral, antitubercular and anticancer activities of some novel thioureas derived from 4-aminobenzohydrazide hydrazones, Marmara Pharm. J., 14(1) (2010) 13-20.
[30] Tatar E., Senkardes S., Sellitepe H.E., Kucukguzel S.G., Karaoglu S.A., Bozdeveci A., De Clercq E., Pannecouque C., Ben Hadda T., Kucukguzel I., Synthesis, and prediction of molecular properties and antimicrobial activity of some acylhydrazones derived from N-(arylsulfonyl)methionine, Turkish J. Chem., 40(3) (2016) 510-534.
[31] Han M.I., Bekci H., Cumaoglu A., Kucukguzel, S.G., Synthesis and characterization of 1,2,4-triazole-containing hydrazide-hydrazones derived from (S)-naproxen as anticancer agents, Marmara Pharm. J., 22(4) (2018) 559-569.
[32] Senkardes S., Kiymaci M.E., Kale K., Kozanoglu I.M., Kaskatepe B., Kucukguzel S.G., Synthesis, structural elucidation and biological activities of some novel sulfonyl hydrazones as antibacterial agents, J. Res. Pharm., 25(2) (2021) 135-141.
[33] Aydin S., Kaushik-Basu N., Arora P., Basu A., Nichols D.B., Talele T.T., Akkurt M., Celik I., Buyukgungor O., Kucukguzel S.G., Microwave assisted synthesis of some novel flurbiprofen hydrazide-hydrazones as anti-HCV NS5B and anticancer agents, Marmara Pharm. J., 17(1) (2013) 26-34.
[34] Han M.İ., Atalay P., Tunç C.Ü., Ünal G., Dayan S., Aydın Ö., Küçükgüzel Ş.G., Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models, Bioorg. Med. Chem., 1(37) (2021) 116097.
[35] Senkardes S., Tatar E., Nepravishta R., Cela D., Paci M., Bingöl-Ozakpinar O., Sekerler T., De Clercq E., Pannecouque C., Kucukguzel S.G., Synthesis and Biological Activity of N-(arylsulfonyl) Valine Hydrazones and Assistance of NMR Spectroscopy for Definitive 3D Structure, Lett. Drug Design&Discov., 16(9) (2019) 974-983.
[36] SwissTargetPrediction. Swiss Institute of Bioinformatics, (2021), Retrieved 12 April, 2022 from http://www.swisstargetprediction.ch/

Year 2022, , 384 - 390, 30.09.2022

Göknil Coşkun , Akın Aklamuz Ufuk İnce Mert Ülgen

https://doi.org/10.17776/csj.1105811

Cited By: 2

Abstract

Project Number

This study was granted by TUBITAK 2209-A 2021/1 1919B012100499

References

[1] Zheng H., Li H., Deng H., Fang W., Huang X., Qiao J., Tong Y., Near İnfrared Light-Responsive And Drug-Loaded Black Phosphorus Nanosheets For Antibacterial Applications, Colloids Surf B Biointerfaces, 214 (2022) 112433.
[2] Theuretzbacher U., Resistance drives antibacterial drug development, Curr. Opin. Pharmacol, 11(5) (2011) 433-8.
[3] Kaplan Ö., Gökşen N. Biosynthesis of silver nanoparticles from Teucrioside and investigation of its antibacterial activity, Cumhuriyet Sci. J., 42 (1) (2021) 60-67.
[4] Aşan Özüsağlam M. , Tacer S. , Boulechfar S., Zellaguı A. An Investigation of the Bactericidal and Fungicidal Effects of Algerian Propolis Extracts and Essential Oils., Cumhuriyet Sci. J., 43 (1) (2022) 14-19.
[5] Akgül Ö., Akgünlü Ç., Biler H., Ateş A., Ermertcan Ş. Antimicrobial activity screening of a series of taurine derivatives, Cumhuriyet Science J, 42 (4) (2021) 781-788.
[6] Lister P.D., The role of pharmacodynamic research in the assessment and development of new antibacterial drugs, Biochem Pharmacol, 71(7) (2006) 1057-65.
[7] Boulebda H., Zinea Y., Khodjaa I.A., Mermer A., Demir A., Debache A., Synthesis and radical scavenging activity of new phenolic hydrazone/hydrazide derivatives: Experimental and theoretical studies, J. Mol. Struct., 1249 (2022) 131546.
[8] Komurcu S.G., Rollas S., Ulgen M., Gorrod J.W., Cevikbas A., Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism, Boll Chim. Farm., 134(7) (1995) 375-9.
[9] Ulgen M., Durgun B.B., Rollas S., Gorrod J.W., The in vitro hepatic microsomal metabolism of benzoic acid benzylidenehydrazide, Drug Metabol Drug Interact, 13(4) (1997) 285-94.
[10] P. Vijaya G., Sundaraselvan., Synthesis, characterization, PASS analysis and ADMET properties of oxazolone ring containing hydrazone derivatives, Materials Today: Proceedings, 48 (2022) 502–507.
[11] Chen J., Lu W., Chen H., Bian X., Yang G., A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants, Biol. Pharm. Bull, 42(2) (2019) 231-246.
[12] Yamada H., Kojo M., Nakahara T., Murakami K., Kakima T., Ichiba H., Yajima T., Fukushima T., Development of a fluorescent chelating ligand for scandium ion having a Schiff base moiety, Spectrochim. Acta A. Mol. Biomol. Spectrosc., 90 (2012) 72-7.
[13] Clinical and L.S. Institute, Performance standards for antimicrobial susceptibility testing, Clinical and Laboratory Standards Institute Wayne, PA. (2017).
[14] Wayne, P., Clinical and Laboratory Standards Institute: Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, CLSI Document M27-A3 and Supplement S., 3 (2008) 6-12.
[15] Shi L., Ge H.M., Tan S.H., Li H.Q., Song Y.C., Zhu H.L., Tan R.X., Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde, Eur. J. Med. Chem., 42 (4) (2007) 558-64.
[16] Rollas S., Küçükgüzel S.G., Biological activities of hydrazone derivatives, Molecules, 12(8) (2007) 1910-39.
[17] Küçükgüzel S.G., Mazi A., Sahin F., Oztürk S., Stables J., Synthesis and biological activities of diflunisal hydrazide-hydrazones, Eur. J. Med. Chem., 38 (11-12) (2003) 1005-13.
[18] Şenkardeş S., Kaushik-Basu N., Durmaz İ., Manvar D., Basu A., Atalay R., Küçükgüzel Ş.G., Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors, Eur. J. Med. Chem., 27(108) (2016) 301-308.
[19] Rollas S., Kucukguzel S.G., Hydrazone, amide, carbamate, macromolecular and other prodrugs of doxorubicin, Open Drug Delivery Journal, 2 (2008) 77-85.
[20] Küçükgüzel Ş.G., Koç D., Çıkla-Süzgün P., Özsavcı D., Bingöl-Özakpınar Ö., Mega-Tiber P., Orun O., Erzincan P., Sağ-Erdem S., Şahin F., Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells, Arch. Pharm. (Weinheim), 348(10) (2015) 730-42.
[21] Küçükgüzel S.G., Rollas S.. Synthesis, characterization of novel coupling products and 4-arylhydrazono-2-pyrazoline-5-ones as potential antimycobacterial agents, Farmaco, 57(7) (2002) 583-7.
[22] Han M.I., Guler G., Temel Y., Sadik K., Kucukguzel S.G., Synthesis and antibacterial activity of new hydrazide-hydrazones derived from Benzocaine, Marmara Pharm. J., 21(4) (2017) 961-966.
[23] Çıkla-Süzgün P., Küçükgüzel Ş.G., Recent Advances in Apoptosis: THE Role of Hydrazones, Mini Rev. Med. Chem., 19(17) (2019) 1427-1442.
[24] Şenkardeş S., Han M.İ., Kulabaş N., Abbak M., Çevik Ö., Küçükgüzel İ., Küçükgüzel Ş.G., Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors, Mol. Divers, 24(3) (2020) 673-689.
[25] Çıkla P., Özsavcı D., Bingöl-Özakpınar Ö., Şener A., Çevik Ö., Özbaş-Turan S., Akbuğa J., Şahin F., Küçükgüzel Ş.G., Synthesis, cytotoxicity, and pro-apoptosis activity of etodolac hydrazide derivatives as anticancer agents, Arch. Pharm. (Weinheim), 346(5) (2013) 367-79.
[26] Hamzacebi M.C., Rollas S., Kucukguzel, S.G., Kocyigit-Kaymakcioglu B., Synthesis and structure elucidation of hydrazones derived from N-(2,4-dimethylphenyl)-3-oxobutanamide, ARKIVOC (Gainesville, FL, United States), (12) (2008) 188-194.
[27] Kucukguzel S.G., Rollas S., Kucukguzel I., Kiraz M., Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones, Eur. J. Med. Chem., 34(12) (1999) 1093-1100.
[28] Koc H.C., Atlihan I., Mega-TIber P., Orun O., Kucukguzel S.G., Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents, J. Res. Pharm., 26(1) (2022) 1-12.
[29] Cikla P., Kucukguzel G., Kucukguzel I., Rollas S., De Clercq E., Pannecouque C., Andrei G., Snoeck R., Sahin F., Bayrak O.F., Synthesis and evaluation of antiviral, antitubercular and anticancer activities of some novel thioureas derived from 4-aminobenzohydrazide hydrazones, Marmara Pharm. J., 14(1) (2010) 13-20.
[30] Tatar E., Senkardes S., Sellitepe H.E., Kucukguzel S.G., Karaoglu S.A., Bozdeveci A., De Clercq E., Pannecouque C., Ben Hadda T., Kucukguzel I., Synthesis, and prediction of molecular properties and antimicrobial activity of some acylhydrazones derived from N-(arylsulfonyl)methionine, Turkish J. Chem., 40(3) (2016) 510-534.
[31] Han M.I., Bekci H., Cumaoglu A., Kucukguzel, S.G., Synthesis and characterization of 1,2,4-triazole-containing hydrazide-hydrazones derived from (S)-naproxen as anticancer agents, Marmara Pharm. J., 22(4) (2018) 559-569.
[32] Senkardes S., Kiymaci M.E., Kale K., Kozanoglu I.M., Kaskatepe B., Kucukguzel S.G., Synthesis, structural elucidation and biological activities of some novel sulfonyl hydrazones as antibacterial agents, J. Res. Pharm., 25(2) (2021) 135-141.
[33] Aydin S., Kaushik-Basu N., Arora P., Basu A., Nichols D.B., Talele T.T., Akkurt M., Celik I., Buyukgungor O., Kucukguzel S.G., Microwave assisted synthesis of some novel flurbiprofen hydrazide-hydrazones as anti-HCV NS5B and anticancer agents, Marmara Pharm. J., 17(1) (2013) 26-34.
[34] Han M.İ., Atalay P., Tunç C.Ü., Ünal G., Dayan S., Aydın Ö., Küçükgüzel Ş.G., Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models, Bioorg. Med. Chem., 1(37) (2021) 116097.
[35] Senkardes S., Tatar E., Nepravishta R., Cela D., Paci M., Bingöl-Ozakpinar O., Sekerler T., De Clercq E., Pannecouque C., Kucukguzel S.G., Synthesis and Biological Activity of N-(arylsulfonyl) Valine Hydrazones and Assistance of NMR Spectroscopy for Definitive 3D Structure, Lett. Drug Design&Discov., 16(9) (2019) 974-983.
[36] SwissTargetPrediction. Swiss Institute of Bioinformatics, (2021), Retrieved 12 April, 2022 from http://www.swisstargetprediction.ch/

There are 36 citations in total.

Details

Primary Language	English
Subjects	Pharmacology and Pharmaceutical Sciences
Journal Section	Natural Sciences
Authors	Göknil Coşkun 0000-0001-5168-3866 Akın Aklamuz 0000-0003-2374-3061 Ufuk İnce 0000-0002-7316-4802 Mert Ülgen 0000-0003-4913-4950
Project Number	This study was granted by TUBITAK 2209-A 2021/1 1919B012100499
Publication Date	September 30, 2022
Submission Date	April 22, 2022
Acceptance Date	June 30, 2022
Published in Issue	Year 2022

Cite

APA	Coşkun, G., Aklamuz, A., İnce, U., Ülgen, M. (2022). Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds. Cumhuriyet Science Journal, 43(3), 384-390. https://doi.org/10.17776/csj.1105811

Cited By

Preparation, in vitro and in silico antioxidant and antibacterial studies of 4-aminoacetanilide azo derivatives

Journal of the Indian Chemical Society

https://doi.org/10.1016/j.jics.2024.101341

Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer

Pharmaceutics

https://doi.org/10.3390/pharmaceutics15051441

Article Files

Full Text