SHAVKAT RUSTAMOV

Scopus Publications

Mechanism of vasorelaxant effect of the indole alkaloid 12-hydroxynorfluorocurarine hydrochloride on aortic smooth muscle contraction
Ibragimov Eldor Bakhtiyor Ugli, Zhumaev Inoyat Zulfiqorovich, Zaripov Abdisalim Abdikarimovich, Usmanov Pulat Bekmuratovich, Rustamov Shavkat Yusubovich, Esimbetov Adilbay Tlepovich, Adizov Shahobiddin Mukhammadovich, Kurbanov Abduburkhan Kuzibayevich
Journal of Applied Pharmaceutical Science, 2026
This article examines the mechanism of action of 12-hydroxynorfluorocurarine hydrochloride on vascular contractile activity. The studies were conducted in vitro using rat aortic rings. The isometric force of the contractile force of the rings was measured using an FT-03 force transducer (Grass Instrument, USA). 12-Hydroxynorfluorocurarine hydrochloride produced a dose-dependent vasorelaxant response on phenylephrine-induced aortic ring contractility, with the vasorelaxant response being reduced in the absence of endothelium. The vasorelaxant effect of 12-hydroxynorfluorocurarine hydrochloride is driven by modulation of the endothelial NO synthase (eNOS), guanylate cyclase (sGC), inward-rectifier K+ channels (Kir), and Ca2+-activated K+ channels. Furthermore, when 50 mM KCl is present, this indole alkaloid was observed to diminish the force of aortic contraction induced by elevated Ca²? ion concentration. 12-Hydroxynorfluorocurarine hydrochloride has been shown to exert potent vasorelaxant effects on rat aortic preparations through both endothelium-dependent and endothelium-independent pathways. It has been shown that the vasorelaxant action of 12- hydroxynorfluorocurarine hydrochloride is mediated by blocking L-type Ca2+ channels via the eNOS/NO/sGC signalling cascade and by activating Kir channels.
Role of F-4 Isoquinoline Alkaloid, Dihydroquercetin Flavonoid and Conjugate DKV-6 in Myocardial RyR2 and SERCA2a under Normal and Hypoxic Conditions
Sadriddin Nurillo ugli Boboev, Inoyat Zulfiqorovich Zhumaev, Pulat Bekmuratovich Usmanov, Abdisalim Abdikarimovich Zaripov, Shavkat Yusubovich Rustamov, Shakhnoza Bakhtiyorovna Qurbonova, Eldor Bakhtiyor ugli Ibragimov, Sardor Bakhtiyor ugli Sobirov, Sherzod Niyatqobulovich Zhurakulov
Biomedical and Pharmacology Journal, 2026
Cardiovascular diseases are among the leading causes of death worldwide, according to the World Health Organization. A key pathogenic factor in ischemia and myocardial infarction is the disruption of Ca²⁺ ion homeostasis and impaired function of the sarcoplasmic reticulum (SR) proteins RyR2 and SERCA2a. Therefore, identifying biologically active substances that modulate Ca²⁺ transport via SERCA2a is of significant scientific and practical importance. In this study, the inotropic effects of the isoquinoline alkaloid F-4, the flavonoid dihydroquercetin (DHQ), and their conjugate DKV-6 were investigated using isolated rat heart papillary muscle preparations. Mechanographic results showed that F-4 (120 μM), DHQ (60 μM), and DKV-6 (50 μM) increased papillary muscle contractility by 32.9±3.1%, 51.4±3.4%, and 110.3±3.2%, respectively, compared to control. The post-rest potentiation (PRP) method was employed to assess changes in SR Ca²⁺ levels. The effects of these biologically active compounds (BACs) on RyR2 were studied using tetracaine and ruthenium red, while the role of SERCA2a was evaluated with cyclopiazonic acid (CPA). The results indicated that the positive inotropic effect is closely associated with SERCA2a function. Furthermore, the DKV-6 conjugate exhibits distinct anti-hypoxic activity, effectively counteracting hypoxia-induced impairments in myocardial contractility. Its antiarrhythmic effect appears to be mediated through SERCA2a activation.
Antiarrhythmic Activity of Ethacizine Hydrochloride and its Supramolecular Complexes with Glycyrrhizic Acid and its Monoammonium Salt
Yu. I. Oshchepkova, V. V. Uzbekov, I. Z. Jumayev, Sh. Yu. Rustamov, P. B. Usmanov, Sh. I. Salikhov
Pharmaceutical Chemistry Journal, 2025
Antiarrhythmic Effect of 1-(3'-Bromophenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline Hydrochloride
Qurbonova Shakhnoza Bakhtiyorovna, Zhumaev Inoyat Zulfiqorovich, Boboev Sadriddin Nurillo Ugli, Usmanov Pulat Bekmuratovich, Rustamov Shavkat Yusubovich, Zaripov Abdisalim Abdikarimovich, Zhurakulov Sherzod Niyatkobulovich
Biomedical and Pharmacology Journal, 2025
During the study, the inotropic and antiarrhythmic properties of the alkaloid 1-(3ˊ-Bromophenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (F-25) were investigated. The alkaloid F-25 was shown to exert a negative inotropic effect on the contractile force of rat cardiac papillary muscle, decreasing myocardial contractility by 87.6±4.2% at a concentration of 100 μM compared to the control. To assess the involvement of voltage-gated Na+ channels in providing the negative inotropic effect of the alkaloid F-25, experiments were conducted using lidocaine, a specific blocker of this channel. When the effect of F-25 alkaloid (100 μM) was tested in the existence of lidocaine (IC50=15.4 μM), the amplitude of papillary muscle contraction force was 32.8±3.9%, respectively. The influence of the alkaloid F-25 on Na⁺/Ca²⁺ exchange was examined using NiCl₂, a non-specific blocker of this exchanger. The negative inotropic effect of the alkaloid F-25 (100 μM) on papillary muscle contraction activity in the presence of a 10 mM concentration of NiCl2 in the incubation medium was 42.3±4.2%. The negative inotropic effect of the alkaloid F-25 is exerted mainly by modulating the function of Na+ channels and, in part, the Na+/Ca2+ exchange. The impact of the alkaloid F-25 was also evaluated using an aconitine-induced arrhythmia model, revealing that the compound exhibits strong antiarrhythmic properties
Mechanism of Vasorelaxant Action of Isoquinoline Alkaloid F-19 on Rat Aorta
Abdisalim A. Zaripov, Inoyat Z. Zhumaev, Pulat B. Usmanov, Yulduzkhon T. Mirzaeva, Shavkat Yu. Rustamov, Sadriddin N. Boboev, Adilbay T. Esimbetov, Gulnaz S. Begdullaeva, Sardor B. Sobirov, Eldor B. Ibragimov, Sherzod N. Zhurakulov, Dilbar D. Safarova, Ra'no I. Yusupova
Biomedical and Pharmacology Journal, 2025
The development of cardiovascular diseases is primarily associated with impaired activity of ion transport systems that ensure Ca2+ homeostasis in vascular smooth muscle cells. Modulation of the function of Ca2+ ion transport systems in smooth muscle cells with biologically active compounds allows the development of new approaches to the pharmacological regulation of Ca2+-dependent processes in cardiovascular diseases. This article studies the mechanisms of the vasorelaxant effect of the isoquinoline alkaloid 1-(3¢-Bromo-4¢-hydroxyphenyl-5¢-methoxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (F-19) on the force of aortic ring contraction. It was found that the alkaloid F-19 exerts a concentration-dependent (5-100 μM) potent vasorelaxant effect on the force of aortic ring contraction induced by KCl and PE. The involvement of the L-type Ca2+ channel in the vasorelaxant effect of the alkaloid F-19 was investigated under conditions of incubation with its specific blocker verapamil. It was found that the role of the L-type Ca2+ channel in the vasorelaxant effect of this alkaloid is minor. The effect of the alkaloid F-19 on Ca2+ transport systems in the SR was also investigated. In this case, PE and caffeine-induced transient aortic contraction in the absence of Ca2+ significantly reduced. At the same time, a decrease in the vasorelaxant effect on aortic contractility was observed under the conditions of incubation with the SERCA inhibitor CPA, the alkaloid F-19. The vasorelaxant effect of the alkaloid F-19 on rat aortic smooth muscle contractility is mediated by several complex mechanisms. The vasorelaxant effect of this alkaloid is provided by inhibiting the entry of Ca2+ ions into the cytosol through plasma membrane potential-dependent L-type Ca2+ channels and the exit of Ca2+ ions into the cytosol through the SR Ca2+ transport systems, and by activating SERCA.
Role of RyR2 and SERCA2a in the Cardioprotective Effects of Vincanine and Pyrazoline Alkaloids
Inoyat Zulfiqorovich Zhumaev, Sadriddin Nurillo Ugli Boboev, Pulat Bekmuratovich Usmanov, Shavkat Yusubovich Rustamov, Abdisalim Abdikarimovich Zaripov, Shakhnoza Bakhtiyorovna Qurbonova, Yulduzkhon Takhirjanovna Mirzaeva, Eldor Bakhtiyor Ugli Ibragimov, Adilbay Tlepovich Esimbetov, Shahobiddin Mukhammadovich Adizov
Trends in Sciences, 2025
In the conducted studies, the effect of vincanine and pyrazoline indole alkaloids on cardiac muscle cell sarcoplasmic reticulum (SR) Ca2+-transport systems (RyR2 and SERCA2a) was investigated under normal and hypoxic conditions. The effect of vincanine and pyrazoline on ryanodine receptor (RyR2) was evaluated in the presence of ruthenium red and it was found that the role of RyR2 in the positive inotropic effect of these alkaloids is small. Also, in the presence of cyclopiazonic acid (IC50 = 5.6 µM), an inhibitor of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), the positive inotropic effect of vincanine and pyrazoline alkaloids was reduced. In general, the positive inotropic effects and cardioprotective properties of vincanine and pyrazoline alkaloids are mediated by modulation of SERCA2a function. HIGHLIGHTS Vincanine and pyrazoline indole alkaloids have a positive inotropic effect on the force of papillary muscle contraction of the rat heart. Vincanine and pyrazoline indole alkaloids have a cardioprotective effect and effectively eliminate the disturbances in the papillary muscle contractile activity of the rat heart caused by hypoxia. Vincanine and pyrazoline alkaloids effectively reverse hypoxia-induced SERCA2a dysfunction and normalize changes in rat cardiac papillary muscle contractile activity. GRAPHICAL ABSTRACT
Protective Effect of DHQ-11 against Hypoxia-induced Vasorelaxation
Abdisalim A. Zaripov, Pulat B. Usmanov, Yulduzkhon T. Mirzayeva, Adilbay T. Esimbetov, Shavkat Yu. Rustamov, Sadriddin N. Boboev, Eldor B. Ibragimov, Shakhnoza B. Qurbonova, Sherzod N. Zhurakulov, Inoyat Z. Jumayev
Trends in Sciences, 2024
Hypoxia, or the lack of oxygen, has multiple impacts on the vascular system. The major molecular sensors for hypoxia at the cellular level are hypoxia inducible factor and heme oxygenase. Hypoxia also acts on the vasculature directly conveying its damaging effects through disruption of the control of vascular tone, particularly in the coronary circulation, enhancement of inﬂammatory responses and activation of coagulation pathways. These effects could be particularly detrimental under pathological conditions such as obstructive sleep apnea and other breathing disorders. Introduction: The effect of conjugate 2-(3,4-Dihydroxyphenyl)-6-{[1-(2’-bromo-3’,4’-dimethoxyphenyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H )-yl]methyl}-3,5,7-trihydroxychroman-4-one (DHQ-11) on hypoxia-induced vasorelaxation was investigated in rat aortic rings using standard organ bath techniques. Materials and methods: Hypoxia was stimulated by a superfusion of aortic rings with a glucose-free Krebs solution bubbled with 95 % N2/5 % CO2. The effect of conjugate DHQ-11 was assessed after a 60- min period of hypoxia on aortic rings precontracted with 50 mm KCl or 1µM phenylephrine (PE). The conjugate DHQ-11 significantly attenuated hypoxia-induced vasorelaxation in the endothelium-intact aortic rings precontracted with KCl or PE in a concentration-dependent manner. Results and discussion: This effect of conjugate DHQ-11 was more potent in aortic rings precontracted with PE than those with KCl where it maximally reduced hypoxia-induced vasorelaxation from 44.7 ± 3.7 to 5.4 ± 3.7 and 33.9 ± 3.4 to 10.8 ± 4.2 %, respectively. The removal of the endothelium attenuated the effect of conjugate DHQ-11 on hypoxia-induced vasorelaxation. Similarly, pretreatment of endothelium-intact aortic rings with L-NAME and methylene blue also attenuated the effect of conjugate DHQ-11 on hypoxia-induced vasorelaxation. Furthermore, the blockade of the ATP-sensitive KATP channel with glibenclamide and the calcium-activated large conductance BKCa channel with TEA also significantly attenuated the effect of conjugate DHQ-11 on hypoxia-induced vasorelaxation. Collectively, these results indicated that conjugate DHQ-11 attenuated the hypoxia-induced vasorelaxation suggesting that it alleviated the oxidative damage of vasculature. Conclusions: This effect of conjugate DHQ-11 possible is mediated through several mechanisms including the blockage of the extracellular Ca2+ entry via the voltage-dependent and receptor-operative Ca2+ channels, as well as inhibition of sarcoplasmic reticulum Ca2+ release via the inositol triphosphate pathway. In addition, endothelium and NO/sGC/cGMP/PKG pathway, as well as KATP and BKCa channels most likely participate in protection by conjugate DHQ-11 against hypoxia-induced vasorelaxation.
The Protective Effect of Indole Alkaloid Vincanine Against Hypoxia-Induced Vasorelaxation Model of Rat Aorta
Yulduzkhon T. Mirzayeva, Abdisalim A. Zaripov, Inoyat Z. Zhumaev, Pulat B. Usmanov, Shavkat Yu. Rustamov, Sadriddin N. Boboev, Shakhnoza B. Qurbonova, Eldor B. Ibragimov, Madina K. Musaeva, Sardor B. Sobirov, Shahobiddin M. Adizov
Biomedical and Pharmacology Journal, 2024
Introduction: Using conventional organ bath procedures, the current study sought to determine how vincanine hydrochloride affected vasorelaxation brought on by hypoxia in rat aortic rings. Methods: To induce hypoxia, we used a glucose-free Krebs solution that was infused with 95% N2 and 5% CO2. After 60 minutes of hypoxia, the effect of vincanine was evaluated on aortic rings that were precontracted with either 50 mM KCl or 1 µM phenylephrine (PE). The effect of vincanine was more noticeable in aortic rings that had been precontracted by PE as opposed to KCl. Additionally, when verapamil, a blocker of L-type VDCCs, was preincubated with endothelium-intact aortic rings and KCI was used for precontraction, the effect of vincanine on hypoxia-induced vasorelaxation was significantly reduced. Results: Vincanine inhibited hypoxia-induced vasorelaxation in aortic rings precontracted with PE in a calcium-free buffer. Furthermore, the presence of glibenclamide, a specific inhibitor of ATP-sensitive K+-channels (KATP), and tetraethylammonium chloride (TEA), a nonspecific inhibitor of calcium-activated large conductance K+-channels (BKca), significantly reduced the effect of vincanine on hypoxia-induced vasorelaxation. The removal of the endothelium also had a significant impact on the effect of vincanine on hypoxia-induced vasorelaxation. Conclusion: The present findings showed that alkaloid vincanine isolated from the leaves of Vinca minor H. significantly abolished the hypoxia-induced vasorelaxation in rat aorta. The obtained results suggest that vincanine may protect the rat aorta against hypoxic injuries in the vasculature.
COMPARATIVE STUDY OF ANTIARRHYTHMIC AND INOTROPIC ACTIVITY OF AMIODARONE HYDROCHLORIDE AND ITS COMPLEXES WITH GLYCYRRHIZIC ACID AND MONOAMMONIUM SALT OF GLYCYRRHIZIC ACID
Юлия Игоревна Ощепкова, В. В. Узбеков, И. З. Жумаев, Ш. Ю. Рустамов, П. Б. Усманов, Ш. И. Салихов
Eksperimental Naya I Klinicheskaya Farmakologiya, 2023
Определена антиаритмическая и инотропная активность комплексов амиодарона гидрохлорида (амиодарон ГХ) с глицирризиновой кислотой (ГК) и моноаммониевой солью глицирризиновой кислоты (МАСГК) на моделях CaCl2-индуцированной аритмии в сравнении с амиодароном ГХ. Показано, что амиодарон ГХ, ГК+амиодарон ГХ (8:1) и МАСГК + амиодарон ГХ (8:1) в разной степени вызывают отрицательный инотропный эффект и дозазависимо подавляют сократительную активность сердечной мышцы на 90,7 – 97,3 % (p ≤ 0,01). Амиодарон ГХ и комплексы амиодарона ГХ с ГК и МАСГК эффективно угнетают развитие спонтанных сокращений папиллярной мышцы сердца крысы, вызванные CaCl2, на 30 – 70 % (p ≤ 0,01). При этом эффект комплекса МАСГК + амиодарон ГХ (8:1) на 70 – 40 % (p ≤ 0,01) больше, по сравнению с эффектами амиодарона ГХ и комплекса ГК + амиодарон ГХ (8:1). Усиление отрицательной инотропной и антиаритмической активности комплекса МАСГК + амиодарон ГХ (8:1) может быть обусловлено повышением его липофильности.
Mechanism of Positive Inotropic Effect of Vincanine on Cardiac Muscle Contraction Activity
Inoyat Z. Zhumaev, Sadriddin N. Boboev, Pulat B. Usmanov, Shakhnoza B. Qurbonova, Shavkat Yu. Rustamov, Adilbay T. Esimbetov, Gulnaz S. Begdullaeva, Abdisalim A. Zaripov, Shahobiddin M. Adizov
Biomedical and Pharmacology Journal, 2022
In the present study, the dose-dependent effect of the alkaloid vincanine on the contractile activity of rat heart papillary muscle was investigated and it was found to increase the force of muscle contraction at all concentrations. The half-maximal inotropic effect concentration (ED50) of vincanine was 21.8 μM, respectively. Studies of the effect of this alkaloid on the cardiomyocyte Na+-channel in the presence of its blocker lidocaine showed that the positive inotropic effect of vincanine does not involve the Na+-channel. When studying the effect of vincanine on Сa2+L-channels in the presence of nifedipine (IC50=0.01 μM), the positive inotropic effect of vincanine (50 μM) alkaloid was partially reduced. In general, it was found that the positive inotropic effect of vincanine on the force of papillary muscle contraction is partially mediated by Сa2+L-channels and mainly Na+/Сa2+ exchange.
The combined inotropic and vasorelaxant effect of DHQ-11, a conjugate of flavonoid dihydroquercetin with isoquinoline alkaloid 1-aryl-6,7-dimethoxy-1,2.3,4-tetrahydroisoquinoline
Pulat B. Usmanov, Inoyat Z. Jumayev, Shavkat Yu. Rustamov, Abdisalim A. Zaripov, Adilbay T. Esimbetov, Sherzod N. Zhurakulov, Valentina I. Vinogradova
Biomedical and Pharmacology Journal, 2021
Comparative inotropic effects of the some isoquinoline alkaloids
Inoyat Jumayev, Pulat Usmanov, Shavkat Rustamov, Sherzod Zhurakulov
Biomedical and Pharmacology Journal, 2020

SHAVKAT RUSTAMOV

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