Razi Journal of Medical Sciences

fa سنتز و بررسی اثر سایتوکسیک مشتقات جدیدی از 2 -آریل ایندول حاوی تیوسمی کاربازون و تری آزول در برابر سلول‌های سرطانی با استفاده از روش MTT Cytotoxic Evaluation of Synthesized Novel Derivatives of 2-Aryl Indole Containing Thiosemicarbazone and Triazole Moeitoes, Against Cancer Cells Using MTT Assay داروسازی Pharmacy پژوهشي Research <div style="text-align: justify;">زمینه و هدف: شیمی درمانی سرطان با مشکلات عدیدهای از جمله عدم تحمل بیمار یا مقاوم شدن سلولهای سرطانی به ترکیبات و داروهای مورد مصرف مواجه است. با توجه به اینکه ساختارهای حاوی حلقه ایندول و سمی کاربازون و تیازولها قبلاً اثرات بیولوژیک متفاوتی از خود نشان دادهاند. در این مقاله قرار است هیبریدهایی از این ساختارهای شیمیایی طراحی و اثرات آنها بررسی شود شاید بتوان به ترکیبات جدیدی دست یافت تا به پارهای از مشکلات در سر راه شیمی درمانی چیره گشت. هدف از این مقاله سنتز و بررسی خاصیت ضد سرطانی ترکیبات هیبریدی جدید از ایندول متصل به فارماکوفورهای تری آزول و تیوسمی کاربازون با استفاده از روش کلیک است. روش کار: مشتقات ایندول و 3،2،1-تری آزولها و تیوسمی کاربازون به دلیل خواص بیولوژیکی متنوع از جمله ضد التهاب، ضد باکتری، ضدHIV، ضد قارچ و ضد سرطان از اهمیت ویژهای برخوردارند. در این مقاله، از واکنش کلیک جهت سنتز ترکیبات استفاده شد واکنشهای کلیک در شرایط ملایم در حضور حلال ارزان قیمت و زمان کوتاه انجام شده و محصول با راندمان و خلوص بالا (کمترین میزان محصولات جانبی) به دست میآید لذا با بهره گرفتن از واکنش کلیک مشتقات جدیدی از 3،2،1-تری آزولهای متصل به سیستم 2-آریل-1H-ایندول-3-استخلافدار بین دو ترکیب 2-آریل-1-پروپ-2-اینیل-1H-ایندول-3-استخلافدار و آزیدهای آروماتیک در حضور کاتالیزگر مس(ΙΙ) استات و سدیم آسکوربات در حلال اتانول سنتز گردید. هم چنین یکسری مشتقات جدیدی از 2- آریل -1H-ایندول -3- استخلاف دار هیبرید شده با تیوسمی کاربازون و تری آزول نیز در حضور کاتالیزگر پارا تولوئن سولفونیک اسید در حلال اتانول سنتز گردید و ساختار تمام ترکیبات سنتز شده به وسیلهی آنالیزهای IR، H-NMR1 و 13 C-NMR تایید گردید. یافته‌ها: در راستای حل مشکل سرطان از ترکیبات با فارماکوفور های مختلف از جمله: ایندول، تری آزول (به دلیل وجود در بسیاری از ترکیبات سیتوتوکسیک و ضد میکروبی و اثر بخشی این اسکلت) و تیوسمی کاربازون و اتصال این سه فارماکوفور به یکدیگر جهت یافتن ترکیبات جدید که دارای سمیت سلولی احتمالی باشند استفاده گردید. فعالیت سیتوتوکسیک این ترکیبات بر روی دو رده سلولیHela  و MCF-7  توسط روش MTT مورد بررسی قرار گرفت. نتیجه‌گیری: نتایج نشان داد که ترکیبات مورد بررسی  برروی رده سلولیHela ، صرفاً در بالا ترین غلظت (µM1000) به میزان قابل توجهی اثرسیتوتوکسیک داشتهاند و در سایر غلظت ها فاقد اثر بودهاند و در بعضی از موارد از جمله اثر بر روی رده MCF-7 به نظر میرسد که ترکیبات حتی رشد سلول را افزایش نیز دادهاند که این افزایش رشد احتمال دارد به خاطر تشابه ساختاری بعضی ترکیبات با ساختار های فنلی باشد.</div> <div style="text-align: justify;">Background & Aims: Cancer chemotherapy is facing many problems such as patients' intolerance or resistance of cancer cells to the used compounds and drugs. In this regard, researchers are continuously trying to design new anti-cancer compounds and use them. Test to find a combination that can overcome these problems. Considering that structures containing Indole rings and toxic Carbazone and Thiazoles have already shown different biological effects. In this article, hybrids of these chemical structures will be designed and their effects will be investigated, maybe new compounds can be obtained to overcome some of the problems in the way of chemotherapy. The purpose of this paper is to synthesize and investigate the anticancer properties of new hybrid compounds of Indole attached to Triazole and thiosemicarbazone pharmacophores using the click method. Derivatives of indole and 3,2,1-triazoles and thiosemicarbazone are of special importance due to various biological properties such as anti-inflammatory, antibacterial, anti-HIV, anti-fungal, and anti-cancer. In this research, new derivatives of 3, 2,1-triazoles attached to 2-aryl-1H-indole-3-substituted system by click reaction between 2-aryl-1-prop-2-ynyl-1H-indole-3-substituted and azide Aromatics were synthesized in the presence of copper(II) acetate and sodium ascorbate catalyst in ethanol solvent. Also, a series of new derivatives of 2-aryl-1H-indole-3-substituted hybridized with thiosemicarbazone and triazole were synthesized in the presence of Paratoluenesulfonic acid catalyst in ethanol solvent, and the cytotoxic activity of these compounds on Hela and MCF cell lines. Compounds with heterocyclic structures, because they exist in many natural products and exhibit different physicochemical properties, also have different biological effects, which has diversified their use in the treatment of various diseases. Cancer chemotherapy is faced with many problems such as patient intolerance or resistance of cancer cells to the used compounds and drugs. In this regard, researchers are constantly trying to design new anti-cancer compounds and test them to find a combination. achieve that can overcome these problems. They are considering that structures containing indole rings and toxic carbazone and thiazoles have already shown different biological effects. In this article, hybrids of these chemical structures will be designed and their effects will be investigated, maybe new compounds can be obtained to overcome some of the problems in chemotherapy. Derivatives of indole and 3,2,1-triazoles and thiosemicarbazone are of special importance due to their various biological properties, including anti-inflammatory, antibacterial, anti-HIV, anti-fungal, and anti-cancer. In this research, new derivatives of 3, 2,1-triazoles attached to 2-aryl-1H-indole-3-substituted system by click reaction between 2-aryl-1-prop-2-ynyl-1H-indole-3-substituted and azide Aromatics were synthesized in the presence of copper(II) acetate and sodium ascorbate catalyst in ethanol solvent. Also, a series of new derivatives of 2-aryl-1H-indole-3-substituted hybridized with thiosemicarbazone and triazole were synthesized in the presence of para toluene sulfonic acid catalyst in ethanol solvent, and the cytotoxic activity of these compounds on Hela and MCF cell lines. 7 was investigated. To solve the problem of cancer from compounds with different pharmacophores such as indole, triazole (due to the presence in many cytotoxic and antimicrobial compounds and the effectiveness of this skeleton), and thiosemicarbazone and connecting these three pharmacophores to find new compounds that have possible cytotoxicity were used. Methods: Derivatives of Indole and 3,2,1-triazoles and thiosemicarbazone are of special importance due to various biological properties such as anti-inflammatory, antibacterial, anti-HIV, anti-fungal, and anti-cancer. In this paper, the click reaction was used for the synthesis of compounds. The click reactions were performed under mild conditions in the presence of cheap solvent and in a short time, and the product with high efficiency and purity (lowest amount of side products) is obtained. Click reaction of new derivatives of 3,2,1-triazoles attached to the 2-aryl-1H-indole-3-substituted system between 2-aryl-1-prop-2-ynyl-1H-indole-3-substituted Decompound Aromatic Azides were synthesized in the presence of copper(II) acetate and sodium ascorbate catalyst in ethanol solvent. Also, a series of new derivatives of 2-aryl-1H-indole-3-substituted hybridized with thiosemicarbazone and Triazole were also synthesized in the presence of Paratoluenesulfonic acid catalyst in ethanol solvent, and the structure of all the synthesized compounds was analyzed by IR, H-NMR1 and 13 C-NMR were confirmed. Results: In order to solve the problem of cancer from compounds with different Pharmacophores such as Indole, Triazole (due to the presence in many cytotoxic and antimicrobial compounds and the effectiveness of this skeleton), and thiosemicarbazone and connecting these three pharmacophores to each other It was used to find new compounds that have possible cytotoxicity. The cytotoxic activity of these compounds on Hela and MCF-7 cell lines was evaluated by the MTT method. Conclusion: The results showed that the investigated compounds had a significant cytotoxic effect on the Hela cell line only at the highest concentration (1000 µM) and had no effect at other concentrations and in some cases, including the effect on the MCF line. It seems that the compounds even increased cell growth. This increase in growth is likely to be due to the structural similarity of some compounds with phenolic structures, which has been shown in previous studies that phenolic groups act similar to estrogenic compounds and therefore can mimic growth. According to the results, these compounds can be considered as non-toxic agents for other therapeutic applications.</div> 3,2,1-تری آزول‌ها, واکنش کلیک, تیوسمی کاربازید, سمیت سلولی, آزمون MTT, ایندول 3,2,1-Triazoles, Click Reaction,Thiosemicarbazide,Cytotoxicity, MTT Test, Indole 215 222 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7535-1&slc_lang=fa&sid=1 Mahsa Hajjarzadeh مهسا حجارزاده mahsahajjarzadeh171374@gmail.com 3900319475328460077443 0009-0005-2669-173X Yes Department of Chemistry, Shahreza Branch, Islamic Azad University, Shahreza, Iran گروه شیمی، واحد شهرضا، دانشگاه آزاد اسلامی، شهرضا، ایران