Some oxoimidazolidine and cyanoguanidine compounds: Toxicological efficacy and structure-activity relationships studies

Current Chemistry Letters 12 (2023) 695–704 Contents lists available at GrowingScience Current Chemistry Letters homepage: www.GrowingScience.com Some oxoimidazolidine and cyanoguanidine compounds: Toxicological efficacy and structure-activity relationships studies Shaban A. A. Abdel-Raheema, Ali M. Drarb*, Bahgat R. M. Husseinc* and Amr H. Moustafac,d a Soils, Water, and Environment Research Institute, Agricultural Research Center, Giza, Egypt Plant Protection Research Institute, Agriculture Research Center, Dokki, Giza, Egypt c Department of Chemistry, Faculty of Science, Sohag University, Sohag, 82524, Egypt d Faculty of Science, King Salman International University, Ras sudr, Sinai 46612, Egypt b CHRONICLE Article history: Received December 25, 2022 Received in revised form January 28, 2023 Accepted May 16, 2023 Available online May 16, 2023 Keywords: Oxoimidazolidine and cyanoguanidine Toxicity Aphis craccivora Koch Structure-Activity Relationships (SAR) ABSTRACT This manuscript reports the preparation and toxicological efficacy testing of nine oxoimidazolidine and cyanoguanidine compounds (3a, 3b, 3c, 3d, 3e, 3f, 3g 4a, and 4b) against cowpea aphid, Aphis craccivora Koch. Bioefficacy data revealed that the tested compounds exhibited a range of toxicological activities against these insects, with compound 3b being the most toxic and compound 4a being the least effective. The LC50 value of compound 3b was 1.72 ppm for adults and 0.02 ppm against nymphs of the cowpea aphid, while the LC50 value of compound 4a was 72.51 ppm for adults and 18.02 ppm against nymphs. The manuscript also presents the structure-activity relationships of these compounds. These results provide valuable insights into the development of effective pest control agents for the management of such insects. © 2023 by the authors; licensee Growing Science, Canada. Graphical Abstract 1. Introduction Oxoimidazolidine and cyanoguanidine compounds represent two classes of organic chemicals that have been the subject of extensive research due to their various bioactive properties in different fields such as pharmaceuticals, agrochemicals, and materials science, in addition to the applications of the other organic compounds.1-20 These compounds have demonstrated significant biological activities, making them attractive targets for the development of novel therapeutic agents and pesticides.One such application is in the control of agricultural pests, such as the cowpea aphid, Aphis craccivora Koch, a major pest affecting important legume crops worldwide.Oxoimidazolidines are a class of heterocyclic compounds * Corresponding author. E-mail address (A. M. Drar) © 2023 by the authors; licensee Growing Science, Canada doi: 10.5267/j.ccl.2023.5.005 696 containing a five-membered ring with two non-adjacent nitrogen atoms, an oxygen atom, and a carbonyl group. These compounds have attracted considerable attention due to their broad spectrum of biological activities, including antiviral, antitubercular,and antifungal properties.21-22 In recent years, research has focused on developing novel synthetic strategies for the preparation of oxoimidazolidine derivatives and exploring their potential applications in drug discovery and development.23 Cyanoguanidines are organic compounds featuring a guanidine moiety with a cyano group attached to one of the nitrogen atoms. These compounds have been widely studied for their pharmacological properties, such as anti-inflammatory and antihypertensive activities.24-25 Cyanoguanidines also serve as key intermediates in the synthesis of many bioactive compounds and have been utilized in the development of novel pesticides and herbicides.26 Plant insect diseases have posed serious risks to crops in the world and caused a severe loss throughout the world.27 The cowpea aphid, scientifically known as Aphis craccivora Koch, is a small insect that feeds on the sap of plants in the legume family, including cowpeas, soybeans, and alfalfa. This pest is known for its destructive impact on crops, as it can cause significant yield lossesby directly feeding on plant sap and transmitting plant viruses and reduce the quality of the affected plants.28-29 The cowpea aphid is found in many parts of the world, and is considered a major agricultural pest in many regions.Despite its small size, this insect can reproduce rapidly and infest crops in large numbers, making it a significant threat to food security and agricultural sustainability.Understanding the biology, behavior, and ecology of the cowpea aphid is essential for developing effective strategies to manage this pest and minimize its impact on crop production. Current management strategies for A. craccivora include the use of synthetic insecticides and biological control agents. However, issues such as resistance development and environmental concerns have necessitated the search for new bioactive compounds acting as possible insecticides.Given the potential biological activities of oxoimidazolidine and cyanoguanidine compounds, further research exploring their prospective as new agents for the control of Aphis craccivora Koch is performed here in this work. 2. Results and Discussion 2.1 Chemistry Herein, the desired compounds (3a, 3b, 3c, 3d, 3e, 3f and 3g) have been prepared in pure state according to literature procedure,17 via the reaction of cyanoguanidine (1) with different reagents, namely, 2,2-dihydroxy-1-phenylethan-1-one (2a); 1-(4-chlorophenyl)-2,2-dihydroxyethan-1-one (2b); 2,2-dihydroxy-1-(4-methylphenyl)ethan-1-one (2c); 2,2dihydroxy-1-(3-methoxyphenyl)ethan-1-one (2d); 2,2-dihydroxy-1-(4-methoxyphenyl)ethan-1-one (2e); 2,2-dihydroxy-1(naphthalen-1-yl)ethan-1-one (2f); 2,2-dihydroxy-1-(naphthalen-2-yl)ethan-1-one (2g), respectively, in ethanol in presence of sodium ethoxide as the best basic catalyst, which was successfully chosen by studying the optimizing various reaction parameters such as: the basic catalyst used, the reaction temperature the suitable solvent, and the cyanoguanidine equivalent amount (Fig. 1).17 O H N O OH HO N (2a) N H H OH HO Cl H N O N (2b) O HO H2N N N (2c) N H H N (3c) O CH3 OH HO EtONa / EtOH H N O H 3C NH N (3b) OH H3C N H H Cl CH3 O N (3a) O O NH O (2d) N N H H N H N (3d) O (1) O OH H3C HO O (2e) H 3C NH N N H H O N (3e) O OH HO O NH (2f) N (3f) O OH HO N N H H O (2g) H NH N H N N (3g) Fig. 1. Synthesis of compounds (3a, 3b, 3c, 3d, 3e, 3f, 3g). S. A. A. Abdel-Raheem et al. / Current Chemistry Letters 12 (2023) 697 Whereas, cyanoguanidine compounds 4a and 4b can be obtained in good yield (55%) according to literature procedure,17 when refluxing of the cyanoguanidine (1) with Arylglyoxals, namely, 2,2-dihydroxy-1-phenylethan-1-one (2a) and 1-(4chlorophenyl)-2,2-dihydroxyethan-1-one (2b) in presence of triethylamine as basic catalyst in methanol. The target products 4a and 4b insoluble in hot ethanol thus, it (...truncated)