Evaluation of In-vivo anti-inflammatory activity of methyl 2-(5-butyl-6-thioxo-1, 3, 5-thiadiazinan-3yl), butanoate : In-vivo anti-inflammatory Activity of Methyl Thiadiazinan-3yl Butanoate

Usman Muhammad; Rahim Ullah; Zakia Subhan; Haji Bahadar; Sher Ahmad; Abdur Rasheed

doi:10.54393/pjhs.v5i03.1338

Authors

Usman Muhammad Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan
Rahim Ullah Department of Pharmacy Sarhad University of Science and Technology, Peshawar, Pakistan
Zakia Subhan Institute of Medical Sciences, Khyber Medical University, Kohat, Pakistan
Haji Bahadar Institute of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan
Sher Ahmad Department of Pharmacy, University of Peshawar, Pakistan
Abdur Rasheed Department of Pharmacy, University of Peshawar, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i03.1338

Keywords:

Inflammation, Inflammatory Mediators, Tissue Injury, Cytokines, Oxidative Stress

Abstract

Inflammation is the body's way of fending off damage. Nonetheless, continuous and increasing inflammation may lead to the development of some chronic illnesses. It is still needed to evaluate new and safe anti-inflammatory therapies because existing medications have major side effects. Objective: To examine a novel compound's anti-inflammatory properties of methyl 2-(5-butyl-6-thioxo-1, 3, 5-thiadiazinan-3yl), butanoate (MBTTB) in albino mice models. Method: To test the anti-inflammatory effects in vivo, carrageenan-induced paw edema in albino mice of both sexes was utilized, and inflammation was measured by using Digital Plethysmometer. After extraction of carrageenan induced paw edematous, tissue level of inflammatory mediators like TNF-α, IL-1β, NF-ĸβ, and cox2 was ascertained by Western Blot analysis. Result: Based on in-vivo anti-inflammatory effects, compound MBTTB was shown to exhibit a maximum percentage inhibition of 16.7% after 1 hour, which is comparable to the standard drugs 12.8%. Following three hours, compound MBTTB showed the highest percentage inhibition of 23.2%, while the standard was 14.5%. Compound MBTTB showed the highest percentage inhibition after five hours (26.2 %), while the standard was 15.4%. The expression of many mediators' proteins, including TNF-α, IL-1β, NF-ĸβ, and COX-2, was ascertained. The computational analysis was carried out to forecast the level of decline of various mediators, including Tumor Necrosis Factor-α, (TNF) Interleukin-1β, NF-ĸβ, and COX-2. Conclusion: When considered as a whole, our current research indicates that MBTTB is a viable option for preventing inflammation in mice that has been caused by carrageenan in edematous paw.

References

Munir A, Khushal A, Saeed K, Sadiq A, Ullah R, Ali G, Ashraf Z, Mughal EU, Jan MS, Rashid U, Hussain I. Synthesis, In-Vitro, In-Vivo Anti-Inflammatory Activities And Molecular Docking Studies Of Acyl And Salicylic Acid Hydrazide Derivatives. Bioorganic Chemistry. 2020 Nov; 104:104168. doi: 10.1016/j.bioorg.2020.104168. DOI: https://doi.org/10.1016/j.bioorg.2020.104168

Khan J, Ali G, Rashid U, Khan R, Jan MS, Ullah R, Ahmad S, Abbasi SW, Khalil AA, Sewell RE. Mechanistic evaluation of a novel cyclohexenone derivative’s functionality against nociception and inflammation: an in-vitro, in-vivo and in-silico approach. European Journal of Pharmacology. 2021 Jul; 902:174091. doi: 10.1016/j.ejphar.2021.174091. DOI: https://doi.org/10.1016/j.ejphar.2021.174091

Ullah R, Ali G, Rasheed A, Subhan F, Khan A, Halim SA, Al-Harrasi A. The 7-Hydroxyflavone Attenuates Chemotherapy-Induced Neuropathic Pain By Targeting Inflammatory Pathway. International Immunopharmacology. 2022 Jun; 107:108674. doi: 10.1016/j.intimp.2022.108674. DOI: https://doi.org/10.1016/j.intimp.2022.108674

Omoigui S. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3–Inflammatory Profile Of Pain Syndromes. Medical hypotheses. 2007 Jan; 69(6):1169-78. doi: 10.1016/j.mehy.2007.06.033. DOI: https://doi.org/10.1016/j.mehy.2007.06.033

Koksal M, Ozkan I, Yarim M, Bilge SS, Bozkurt A, Erol DD. Studies on Synthesis and Anti-inflammatory Activities of Novel 1, 2, 4-Triazolo [3, 4-b]-1, 3, 4-thiadiazines. Rev Chim. 2011 Nov; 62:1069-72.

Naveed M, Khan SZ, Zeeshan S, Khan A, Shal B, Atiq A, Ali H, Ullah R, Khan S. A new cationic palladium (II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models. Naunyn-Schmiedeberg's Archives Of Pharmacology. 2019 Aug; 392:961-77. doi: 10.1007/s00210-019-01645-y. DOI: https://doi.org/10.1007/s00210-019-01645-y

Ullah R, Badshah W, Ali G, Ullah A, Khan SU, Ahmad N, Shahid M, Naveed M, Ullah S, Bangash SA, Althobaiti YS. Cassia artemisiodes attenuates nociceptive and diabetes-induced neuropathic pain modalities apropos antioxidant and anti-inflammatory mechanisms. Biomedicine & Pharmacotherapy. 2022 May; 149:112834. doi: 10.1016/j.biopha.2022.112834. DOI: https://doi.org/10.1016/j.biopha.2022.112834

Ullah R, Ali G, Baseer A, Khan SI, Akram M, Khan S, Ahmad N, Farooq U, Nawaz NK, Shaheen S, Kumari G. Tannic acid inhibits lipopolysaccharide-induced cognitive impairment in adult mice by targeting multiple pathological features. International Immunopharmacology. 2022 Sep; 110:108970. doi: 10.1016/j.intimp.2022.108970. DOI: https://doi.org/10.1016/j.intimp.2022.108970

Ullah R, Ali G, Ahmad N, Akram M, Kumari G, Amin MU, Umar MN. Attenuation of spatial memory in 5xFAD mice by halting cholinesterases, oxidative stress and neuroinflammation using a cyclopentanone derivative. Pharmaceuticals. 2020 Oct; 13(10): 318. doi: 10.3390/ph13100318. DOI: https://doi.org/10.3390/ph13100318

Ullah R, Ali G, Subhan F, Naveed M, Khan A, Khan J, Halim SA, Ahmad N, Al-Harrasi A. Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone. Neurochemistry International. 2021 Mar; 144:104981. doi: 10.1016/j.neuint.2021.104981. DOI: https://doi.org/10.1016/j.neuint.2021.104981

Ambriz-Pérez DL, Leyva-López N, Gutierrez-Grijalva EP, Heredia JB. Phenolic compounds: Natural alternative in inflammation treatment. A Review. Cogent Food & Agriculture. 2016 Dec; 2(1):1131412. doi: 10.1080/23311932.2015.1131412. DOI: https://doi.org/10.1080/23311932.2015.1131412

Ahmed AU. An overview of inflammation: mechanism and consequences. Frontiers in Biology. 2011 Aug; 6(4):274-81. doi: 10.1007/s11515-011-1123-9. DOI: https://doi.org/10.1007/s11515-011-1123-9

Hisamuddin N, Shaik Mossadeq WM, Sulaiman MR, Abas F, Leong SW, Kamarudin N, Ong HM, Ahmad Azmi AF, Ayumi RR, Talib M. Anti-edematogenic and anti-granuloma activity of a synthetic curcuminoid analog, 5-(3, 4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl) penta-2, 4-dien-1-one, in mouse models of inflammation. Molecules. 2019 Jul; 24(14): 2614. doi: 10.3390/molecules24142614. DOI: https://doi.org/10.3390/molecules24142614

Yatam S, Gundla R, Jadav SS, reddy Pedavenkatagari N, Chimakurthy J, Kedam T. Focused library design and synthesis of 2-mercapto benzothiazole linked 1, 2, 4-oxadiazoles as COX-2/5-LOX inhibitors. Journal of Molecular Structure. 2018 May; 1159:193-204.doi: 10.1016/j.molstruc.2018.01.060. DOI: https://doi.org/10.1016/j.molstruc.2018.01.060

El-Moghazy SM, Barsoum FF, Abdel-Rahman HM, Marzouk AA. Synthesis and anti-inflammatory activity of some pyrazole derivatives. Medicinal Chemistry Research. 2012 Aug; 21:1722-33. doi: 10.1007/s00044-011-9691-4. DOI: https://doi.org/10.1007/s00044-011-9691-4

Raheem S, Khan R,Pan X, Ullah R, Halim SA, Khan A, Al-Harrasi A. One pot domino synthesis of new 3, 5-disubstituted-tetrahydro-2H-1, 3, 5-thiadiazine-2-thiones (THTTs) as anti-inflammatory and antinociceptive candidates: A proof from in-vivo to in-vitro and in-silico mechanistic studies. Bioorganic Chemistry. 2022 Oct; 127: 105974. doi: 10.1016/j.bioorg.2022.105974. DOI: https://doi.org/10.1016/j.bioorg.2022.105974

Ahmad N, Subhan F, Islam NU, Shahid M, Ullah N, Ullah R, Khurram M, Amin MU, Akbar S, Ullah I, Sewell RD. Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia. Naunyn-Schmiedeberg's Archives of Pharmacology. 2021 Oct; 394:2033-47. doi: 10.1007/s00210-021-02118-x. DOI: https://doi.org/10.1007/s00210-021-02118-x

Krauze A, Ģērmane S, Eberlin O, Šturms I, Klusā V, Duburs G. Derivatives of 3-cyano-6-phenyl-4-(3-pyridyl)-pyridine-2 (1H)-thione and their neurotropic activity. European journal of medicinal chemistry. 1999 Apr; 34(4) :301-10.doi: 10.1016/S0223-5234(99)80081-6. DOI: https://doi.org/10.1016/S0223-5234(99)80081-6

Khuda F, Haq ZU, Ilahi I, Ullah R, Khan A, Fouad H, Khalil AA, Ullah Z, Sahibzada MU, Shah Y, Abbas M. Synthesis of gold nanoparticles using Sambucus wightiana extract and investigation of its antimicrobial, anti-inflammatory, antioxidant and analgesic activities. Arabian Journal of Chemistry. 2021 Oct; 14(10): 103343. doi: 10.1016/j.arabjc.2021.103343. DOI: https://doi.org/10.1016/j.arabjc.2021.103343

Antonelli M, Kushner I. It's time to redefine inflammation. The FASEB Journal. 2017 May; 31(5): 1787-91. doi: 10.1096/fj.201601326R. DOI: https://doi.org/10.1096/fj.201601326R