Novel hydrazones bearing thiazole scaffold: synthesis, characterization, antimicrobial activities and ADME profile investigation

• Authors: Palak I. Vaja , Bhavesh H. Sarvaiya , Kalpna D. Rakholiya , Mital J. Kaneria , Satish M. Ghelani
• Languages of publication: EN

Abstracts

EN

A novel series of acyl hydrazone derivatives was synthesized by condensing acyl hydrazide of 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid with various substituted aldehydes under reflux, in the presence of a catalytic amount of mineral acid. The reaction progress and purity of the synthesized compounds were monitored by TLC, and their melting points were recorded. Structural characterization was carried out using HRMS, FT-IR, and 1H and 13C NMR, confirming the successful formation of the target compounds. The synthesized compounds were further evaluated for their ADME profiles to assess drug-likeness and pharmacokinetic behavior. Antimicrobial activities were screened against selected bacterial strains, including gram-positive (Staphylococcus aureus, Bacillus cereus) and gram-negative (Salmonella typhimurium, Escherichia coli) organisms, using Tetracycline as a reference standard. The results demonstrated that several compounds exhibited notable antimicrobial properties. Among the tested derivatives, HAS-01 and HAS-03 showed the most promising activity, with significant inhibition against both gram-positive and gram-negative bacteria. These compounds also displayed favorable ADME characteristics, suggesting their potential as lead candidates for further development. The study highlights the importance of the thiazole-based acyl hydrazone scaffold in designing new antimicrobial agents and provides a strong foundation for further optimization and structure–activity relationship studies.

Keywords

EN

ADME; Acyl Hydrazone; Antimicrobial Activity; Thiazole

Discipline

• BIOCHEMISTRY: BIOCHEMISTRY

• Publisher: Scientific Publishing House „DARWIN”
• Journal: World News of Natural Sciences
• Year: 2025
• Volume: 61
• Issue: 2
• Pages: 155-166

Contributors

author

Palak I. Vaja

• Department of Chemistry, Bahauddin Science College, Junagadh, 362001, India

author

Bhavesh H. Sarvaiya

• Department of Chemistry, Bahauddin Science College, Junagadh, 362001, India

author

Kalpna D. Rakholiya

• Department of Biosciences (UGC-CAS), Saurashtra University, Rajkot - 360005, India

author

Mital J. Kaneria

• Department of Biosciences (UGC-CAS), Saurashtra University, Rajkot - 360005, India

author

Satish M. Ghelani

• Department of Chemistry, Bahauddin Science College, Junagadh, 362001, India

References

• [1] Ramimoghadam, Donya, et al. Towards sustainable materials: a review of acylhydrazone chemistry for reversible polymers. Chemistry– A European Journal 30(49) (2024) e202401728
• [2] Bedia KK, Elçin O, Seda U, et al. Synthesis and characterization of novel hydrazide–hydrazones and the study of their structure–antituberculosis activity. Eur J Med Chem, 41(11) (2006) 1253-1261
• [3] Socea LI, Barbuceanu SF, Pahontu EM, et al. Acylhydrazones and Their Biological Activity: A Review. Molecules, 27(24) (2022) 8719
• [4] de Oliveira Carneiro Brum J, França TCC, LaPlante SR, Villar JDF. Synthesis and Biological Activity of Hydrazones and Derivatives: A Review. Mini-Reviews in Medicinal Chemistry, 20(5) (2020) 342-368
• [5] Bo S, Zhang D, Ma M, et al. Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents. Pharmaceuticals, 16(5) (2023) 639
• [6] Kadyan K, Singh R, Sindhu J, et al. Exploring the Structural Versatility and Dynamic Behavior of Acyl/Aroyl Hydrazones: A Comprehensive Review. Top Curr Chem, 383(2) (2025) 18
• [7] Ali A, Khalid M, Rehman MA, et al. An Experimental and Computational Exploration on the Electronic, Spectroscopic, and Reactivity Properties of Novel Halo-Functionalized Hydrazones. ACS Omega, 5(30) (2020) 18907-18918
• [8] Thota S, Rodrigues DA, Pinheiro P de SM, Lima LM, Fraga CAM, Barreiro EJ. N-Acylhydrazones as drugs. Bioorg Med Chem Lett, 28(17) (2018) 2797-2806
• [9] Spiliopoulou N, Constantinou CT, Triandafillidi I, Kokotos CG. Synthetic Approaches to Acyl Hydrazides and Their Use as Synthons in Organic Synthesis. Synthesis (Stuttg), 52(21), (2020) 3219-3230
• [10] Kuhl N, Bode S, Bose RK, et al. Acylhydrazones as Reversible Covalent Crosslinkers for Self‐Healing Polymers. Adv Funct Mater, 25(22) (2015) 3295-3301
• [11] Ghelani SM, Khunt HR, Naliapara YT. Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole Bearing Oxadiazole Derivatives. J Heterocycl Chem, 54(1) (2017) 65-70
• [12] Sarvaiya BH, Vaja PI, Paghdar NA, Ghelani SM. Medicinal perspective of a promising scaffold – dihydropyrimidinones: A review. J Heterocycl Chem, 61(8) (2024) 1325-1348
• [13] Biliz Y, Hasdemir B, Başpınar Küçük H, et al. Novel N -Acyl Hydrazone Compounds as Promising Anticancer Agents: Synthesis and Molecular Docking Studies. ACS Omega, 8(22) (2023) 20073-20084
• [14] Wahbeh J, Milkowski S. The Use of Hydrazones for Biomedical Applications. SLAS Technol, 24(2) (2019) 161-168
• [15] Kassab, Asmaa E. Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present. Archiv der Pharmazie 356(5) (2023) 2200548
• [16] Verma G, Marella A, Shaquiquzzaman M, Akhtar M, Ali M, Alam M. A review exploring biological activities of hydrazones. J Pharm Bioallied Sci, 6(2) (2014) 69
• [17] Shakdofa MME, Shtaiwi MH, Morsy N, Abdel-rassel TMA. Metal complexes of hydrazones and their biological, analytical and catalytic applications: A review. Main Group Chemistry, 13(3) (2014) 187-218
• [18] Burlov AS, Vlasenko VG, Chal’tsev B V., Koshchienko Yu V., Levchenkov SI. Metal Complexes of Aroyl(acyl)benzoylhydrazones of Aromatic Aldehydes and Ketones: Coordination Modes and Properties. Russian Journal of Coordination Chemistry, 47(7) (2021) 439-472
• [19] Tatum LA, Su X, Aprahamian I. Simple Hydrazone Building Blocks for Complicated Functional Materials. Acc Chem Res, 47(7) (2014) 2141-2149
• [20] Hu H, Chen L, Jing T, et al. Novel salicylic acid derivatives connecting to five-membered cycle through an acyl hydrazone bond as multi-stimuli responsive fluorescent smart materials with photoswitching properties. Spectrochim Acta A Mol Biomol Spectrosc, 303 (2023) 123118
• [21] Betancourth, Jolaine Galindo, et al. Versatility of the Amino Group in Hydrazone‐Based Molecular and Supramolecular Systems. European Journal of Organic Chemistry, 2022(28) (2022) e202200228
• [22] Nastasă C, Tiperciuc B, Duma M, Benedec D, Oniga O. New Hydrazones Bearing Thiazole Scaffold: Synthesis, Characterization, Antimicrobial, and Antioxidant Investigation. Molecules, 20(9) (2015) 17325-17338
• [23] Cornea AC, Marc G, Ionuț I, et al. Synthesis, Cytotoxicity and Antioxidant Activity Evaluation of Some Thiazolyl–Catechol Compounds. Antioxidants, 13(8) (2024) 937
• [24] Bansal Y, Silakari O. Multifunctional compounds: Smart molecules for multifactorial diseases. Eur J Med Chem, 76 (2014) 31-42
• [25] Moldovan CM, Oniga O, Pârvu A, et al. Synthesis and anti-inflammatory evaluation of some new acyl-hydrazones bearing 2-aryl-thiazole. Eur J Med Chem, 46(2) (2011) 526-534
• [26] Barbier T, Barbry A, Magand J, et al. Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus. Biomolecules, 2(1) (2022) 131
• [27] Yu X, Shi L, Ke S. Acylhydrazone derivatives as potential anticancer agents: Synthesis, bio-evaluation and mechanism of action. Bioorg Med Chem Lett, 25(24) (2015) 5772-5776
• [28] Tian B, He M, Tang S, et al. Synthesis and antiviral activities of novel acylhydrazone derivatives targeting HIV-1 capsid protein. Bioorg Med Chem Lett, 19(8) (2009) 2162-2167
• [29] Rosado-Quiñones, Angélica M., et al. Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs. Antimicrobial Agents and Chemotherapy 68(6) (2024) e01643-23
• [30] Emami S, Valipour M, Kazemi Komishani F, et al. Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorg Chem, 112 (2021) 104943
• [31] De Melo T, Chelucci R, Pires M, et al. Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. Int J Mol Sci, 15(4) (2014) 5821-5837
• [32] Alharthy RD, Zahra SB, Fatima N, et al. Synthesis and biological evaluation of novel isatin-hydrazide conjugates as potential antidiabetic agents. J Mol Struct, 1288 (2023) 135783
• [33] Narang R, Narasimhan B, Sharma S. A Review on Biological Activities and Chemical Synthesis of Hydrazide Derivatives. Curr Med Chem, 19(4) (2012) 569-612
• [34] Hosangadi BD, Dave RH. An efficient general method for esterification of aromatic carboxylic acids. Tetrahedron Lett, 37(35) (1996) 6375-6378
• [35] Th. Sadeek G, Faiyq Saeed Z, Yakdhan Saleh M. Synthesis and Pharmacological Profile of Hydrazide Compounds. Res J Pharm Technol, 16(2) (2023) 975-982
• [36] Belyaeva ER, Myasoedova Yu V., Ishmuratova NM, Ishmuratov GYu. Synthesis and Biological Activity of N-Acylhydrazones. Russ J Bioorg Chem, 48(6) (2022) 1123-1150
• [37] Lucas AJ, Sproston JL, Barton P, Riley RJ. Estimating human ADME properties, pharmacokinetic parameters and likely clinical dose in drug discovery. Expert Opin Drug Discov, 14(12) (2019) 1313-1327
• [38] Bakchi B, Krishna AD, Sreecharan E, et al. An overview on applications of SwissADME web tool in the design and development of anticancer, antitubercular and antimicrobial agents: A medicinal chemist’s perspective. J Mol Struct 1259 (2022) 132712
• [39] Alyar S, Alyar H, Özdemir Özmen Ü, Aktaş O, Erdem K. Biochemical properties of Schiff bases derived from FDA-approved sulfa drugs: Synthesis, ADME/molecular docking studies, and anticancer activity. J Mol Struct, 1293 (2023) 136167
• [40] Barthe L, Woodley J, Houin G. Gastrointestinal absorption of drugs: methods and studies. Fundam Clin Pharmacol, 13(2) (1999)154-168
• [41] Rakholiya KD, Kaneria MJ, Chanda S V. In vitro Assessment of Novel Antimicrobial from Methanol Extracts of Matured Seed Kernel and Leaf of Mangifera indica L. (Kesar Mango) for Inhibition of Pseudomonas spp. and their Synergistic Potential. American Journal of Drug Discovery and Development, 5(1) (2014) 13-23

• Document Type: article