Journal of Advances in Medical and Biomedical Research

en Recent Advances in the Synthesis and Pharmacological Evaluation of Naproxen Derivatives: A Review Pharmacology Pharmacology مقاله مروری Review Article Naproxen is a medication classified as a non-steroidal anti-inflammatory medicine (NSAID) utilized for its anti-inflammatory properties. The principal functional group in naproxen is the carboxyl group, prompting numerous researchers to modify this group to synthesize novel derivatives of naproxen and investigate their pharmacological efficacy, with the aim of discovering more effective molecules than naproxen. This review examines the methodologies for synthesizing derivatives, emphasizing notable molecules with unique biological activity and the key techniques employed in these investigations. Modification of naproxen to include triazole 5n has been found to enhance the efficacy of the derivative and constitute a potential treatment for prostate cancer. The presence of pyrazole and pyrazoline derivatives 9c and 12f enhances the anti-inflammatory and anti-proliferative activity of the derivative. Research has also found that modifying the carboxyl group of naproxen to derivatives containing heterogeneous sulfur rings, such as thiazole and thiadiazole 14a and 22q, whether as single or fused rings, enhances its anti-inflammatory and analgesic activity. Amines and amino acids 26a, 26b, 29b, 32b, and 33b have also been observed to enhance its anti-inflammatory and analgesic activity. These compounds exhibited high oral absorption and were not carcinogenic or toxic in rodent studies, showing safety and minimal ulceration. The most prominent derivatives that inhibit the COX-2 enzyme are hydrazone derivatives that contain the functional group (-NH-N=CH-), and the substituted m-chlorophenyl 35c emerged as the most inhibitory deriNaproxen is a medication classified as a non-steroidal Anti-Inflammatory Drug (NSAIDs) utilized for its anti-inflammatory properties. The principal functional group in naproxen is the carboxyl group, prompting numerous researchers to modify this group to synthesize novel derivatives of naproxen and investigate their pharmacological efficacy, to discover more effective molecules than naproxen. This review examines the methodologies for synthesizing derivatives, with an emphasis on notable molecules exhibiting unique biological activity and the key techniques employed in these investigations. Modification involves introducing a triazole 5n moiety via transformation of the carboxyl group which has been found to enhance the efficacy of the derivative and constitute a potential treatment for prostate cancer. Some pyrazole and pyrazoline derivatives have shown anti-inflammatory and anti-proliferative activity, like derivative 9c which demonstrated high antioxidant activity due to the presence of a methoxy group (an electron-donating group), which increased its potency. It also exhibited vigorous anti-proliferative activity against MCF-7 cells, with an IC50 value of 1.49 μM. Research has also found that modifying the carboxyl group of naproxen to derivatives containing sulfur-containing heterocyclic rings, such as thiazole and thiadiazole 14a and 22q, whether as single or fused rings, enhances its anti-inflammatory and analgesic activity. Amines and amino acids 26a, 26b, 29b, 32b, and 33b have also been observed to enhance their anti-inflammatory and analgesic activity. These compounds exhibited high oral absorption and were not carcinogenic or toxic in rodent studies, showing safety and minimal ulceration. The most prominent derivatives that inhibit the Cyclooxygenase-2 (COX-2) enzyme are hydrazone derivatives that contain the functional group (-NH-N=CH-), and the substituted m-chlorophenyl 35c emerged as the most inhibitory derivative. Structural modification at the carboxyl group of naproxen yields diverse derivatives with enhanced pharmacological profiles and potential safety advantages over the parent compound. Naproxen, Derivatives Synthesis, Structure–Activity Relationship (SAR), Anti-inflammatory Activity, Analgesic Activity, COX-2 Inhibition, Pharmacological Evaluationvative 13 30 http://journal.zums.ac.ir/browse.php?a_code=A-10-7441-1&slc_lang=en&sid=1 Ahmed J. Al-Musawi ahmedjaafar@uomisan.edu.iq 5200319475328460087521 5200319475328460087521 Yes Department of Chemistry, College of Science, University of Misan, Maysan, 62001, Iraq Abdulateef Abdulkadhim Mashaf abdalatif451992@gmail.com 5200319475328460087522 5200319475328460087522 No Ministry of Education, General Directorate of Education in Misan, Maysan, 62001, Iraq Mohammed Amran Mohamran2024@uomanara.edu.iq 5200319475328460087523 5200319475328460087523 No Department of Pharmacy, Al-Manara College for Medical Sciences, Maysan, 62001, Iraq