One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties

Asma Gul; Sobia Ahsan Halim; Ajmal Khan; Rasool Khan; P A N Xian-Dao; Salman Zafar; Noor Akbar; Afnan Jan; Abdullatif Bin Muhsinah; Anar Gojayev; Ahmed Al-Harrasi

doi:10.1016/j.heliyon.2024.e30435

One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties

Heliyon. 2024 Apr 27;10(9):e30435. doi: 10.1016/j.heliyon.2024.e30435. eCollection 2024 May 15.

Authors

Affiliations

¹ Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan.
² Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box-33, Postal Code-616, Birkat Al-Mauz, Nizwa, Sultanate of Oman.
³ Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
⁴ National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Punjab, Pakistan.
⁵ Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, Unites Arab Emirates.
⁶ Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia.
⁷ Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia.
⁸ School of Education, General Education Program, ADA University, Ahmadbey Aghaoghlu Str. 11, Baku, AZ1008, Azerbaijan.

Abstract

The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (1-5), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (6-8), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione (9) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) (10-17) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3, 5 (50 μg/kg), and 8 (50, 100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1, 12-13, and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target μ-opioid receptor (μOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77 μg/mL, respectively. In addition, the predicted ADMET profile of 5, 9, and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization.

Keywords: Anti-bacterial; Anti-nociceptive; Molecular docking; One-pot reaction; Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA); Thiadiazine thiones.