Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition

被引：31

作者：

Shinu, Pottathil ^{[1
]}

Sharma, Manu ^{[2
]}

Gupta, Girdhari Lal ^{[3
]}

Mujwar, Somdutt ^{[4
]}

Kandeel, Mahmoud ^{[5
]}

Kumar, Manish ^{[6
]}

Nair, Anroop B. ^{[7
]}

Goyal, Manoj ^{[8
]}

Singh, Purna ^{[9
]}

Attimarad, Mahesh ^{[7
]}

Venugopala, Katharigatta N. ^{[7
,10
]}

Nagaraja, Sreeharsha ^{[7
,11
]}

Telsang, Mallikarjun ^{[12
]}

Aldhubiab, Bandar E. ^{[7
]}

Morsy, Mohamed A. ^{[7
,13
]}

机构：

[1] King Faisal Univ, Coll Clin Pharm, Dept Biomed Sci, Al Hasa 31982, Saudi Arabia

[2] Natl Forens Sci Univ, Dept Chem, Delhi Campus, New Delhi 110085, India

[3] SVKMs NMIMS Univ, Sch Pharm & Technol Management, Dept Pharmacol, Shirpur 425405, India

[4] Chitkara Univ, Chitkara Coll Pharm, Rajpura 140401, India

[5] King Faisal Univ, Coll Vet Med, Dept Biomed Sci, Al Hasa 31982, Saudi Arabia

[6] Maharishi Markandeshwar Deemed Be Univ, MM Coll Pharm, Ambala 133201, India

[7] King Faisal Univ, Coll Clin Pharm, Dept Pharmaceut Sci, Al Hasa 31982, Saudi Arabia

[8] Imam Abdul Rahman Bin Faisal Univ, Coll Appl Med Sci Jubail, Dept Anesthesia Technol, Jubail Ind City 35816, Saudi Arabia

[9] St James Sch Med, Dept Physiol, Coll Med, The Valley 3872, Anguilla

[10] Durban Univ Technol, Fac Appl Sci, Dept Biotechnol & Food Sci, ZA-4000 Durban, South Africa

[11] Vidya Siri Coll Pharm, Dept Pharmaceut Chem, Off Sarjapura Rd, Bangalore 560035, Karnataka, India

[12] King Faisal Univ, Coll Med, Dept Surg, Al Hasa 31982, Saudi Arabia

[13] Minia Univ, Fac Med, Dept Pharmacol, El Minia 61511, Egypt

来源：

MOLECULES | 2022年 / 27卷 / 20期

关键词：

naproxen; guaiacol; chimera; S-naproxen-4-allylguaiacol; anti-inflammatory; biomedical; treatment; gastro-sparing; ANTIOXIDANT ACTIVITY; STRUCTURAL BASIS; INDOMETHACIN; INJURY; CYCLOOXYGENASE-2; EUGENOL; PATHOGENESIS; INFLAMMATION; MECHANISMS; ULCERATION;

D O I：

10.3390/molecules27206905

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

引用

页数：20

共 52 条

[1] Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies [J].