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Comparative Anti-Inflammatory Profile of Some Cytisine and Tetrahydroisoquinoline Derivatives: Interactions with COX-2 and Histamine H1 Receptors

Azizbek AzamatovDepartment of Pharmacy and Chemistry, Alfraganus University, 2A Yuqori Qoraqamish Street, Yunusobod District, Tashkent 100190, UzbekistanFazilat Kh. MiskinovaDepartment of Physiology and Pathological Physiology, Urgench State Medical Institute, 28 Al-Khorezmi Street, Khorezm Region, Urgench 220100, UzbekistanКурбонов Улугбек АбдурахмоновичYunusov Institute of the Chemistry of Plant SubstancesSherzod ZhurakulovYunusov Institute of the Chemistry of Plant SubstancesKuvonchbek F. KuchimovLaboratory of Chemistry of Alkaloids, Institute of Chemistry of Plant Substances of the Academy of Sciences of the Republic of Uzbekistan, 77 Mirzo Ulugbek Street, Mirzo Ulugbek District, Tashkent 100170, UzbekistanMukaramoy J. ErgashevaPharmaco-Toxicological Research Laboratory, State Institution “Center for Pharmaceutical Products Safety” Under the Ministry of Health of the Republic of Uzbekistan, 16 KakharUmarov Street, Olmazor District, Tashkent 100002, UzbekistanZufar BoboevАбдуразакова Робия ШералиевнаDepartment of Psychiatry, Medical Psychology and Narcology, Samarkand State Medical University, 18 Amir Temur Street, Samarkand 140158, UzbekistanKadir S. ShukurlaevDepartment of Physiology and Pathological Physiology, Urgench State Medical Institute, 28 Al-Khorezmi Street, Khorezm Region, Urgench 220100, UzbekistanValentina I. VinogradovaLaboratory of Chemistry of Alkaloids, Institute of Chemistry of Plant Substances of the Academy of Sciences of the Republic of Uzbekistan, 77 Mirzo Ulugbek Street, Mirzo Ulugbek District, Tashkent 100170, Uzbekistan

2026en

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Annotatsiya

Accumulating evidence indicates extensive crosstalk between prostaglandin- and histamine-mediated signaling pathways. Histamine has been shown to induce COX-2 (Cyclooxygenase-2) expression and stimulate prostaglandin synthesis, whereas prostaglandins potentiate the vascular and inflammatory effects of histamine, creating a positive feedback loop that sustains inflammation. Based on these considerations, in silico molecular docking study of interaction of new cytisine and TGIQ (tetrahydroisoquinoline) derivatives with COX-2 and the histamine H1 receptor was performed. Among the synthesized compounds, compound 1 exhibited the highest binding affinity toward Cyclooxygenase-2 (COX-2). Within the binding pocket of the human H1 histamine receptor, the binding affinity profile differed markedly from that observed for COX-2, with compound 4 exhibiting the highest therapeutic potential and the strongest binding affinity, surpassing all reference compounds. The high anti-inflammatory efficacy of the studied compounds was confirmed in formalin- and histamine rat models. THIQ derivatives were shown to possess a higher anti-inflammatory index than cytisine derivatives. Comparative evaluation of the anti-inflammatory activity of isoquinoline and quinolizidine derivatives revealed that the isoquinoline derivatives possess marked anti-inflammatory properties combined with low toxicity, making them promising candidates for the development of novel, highly effective and safe anti-inflammatory agents for both oral and topical administration.

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DOI: 10.3390/scipharm94040099

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