تهیه مشتقات ایمیدو دی کربونیک دی آمید به روش مایکروویو با استفاده از هیدروکسیدهای لایه ای دوگانه (LDHs) به عنوان کاتالیزوری کارآمد و بررسی اثر ضدایدز آن ها: مطالعه تجربی و نظری

نوع مقاله : مقاله علمی پژوهشی

نویسندگان

1 گروه شیمی آلی، دانشگاه آزاد اسلامی واحد تهران شمال، تهران، ایران

2 گروه شیمی دارویی، دانشکده داروسازی، دانشگاه علوم پزشکی زنجان، زنجان، ایران

3 گروه شیمی دارویی، دانشکده داروسازی، دانشگاه شهید بهشتی، تهران، ایران

4 مرکز تحقیقات علوم داروئی دریایی، دانشگاه علوم پزشکی جندی شاپور اهواز، اهواز، ایران

چکیده

در این مطالعه، با هدف گسترش شیمی سبز، کاتالیزوری بر پایه هیدروکسیدهای لایه ای دوگانه (LDHs) متصل به هگزامتیلن-۱و۶-دی ایزوسیانات (HMDI) و اسید سیتریک (LDHs-g-HMDI-Citric acid) تهیه و با استفاده از تکنیک‌های مختلف FT-IR، XRD، EDX، SEM، TGA و DTG شناسایی گردید. فعالیت کاتالیستی این کاتالیزور هتروژن قابل بازیافت برای سنتز مشتقات جدید ایمیدو دی کربونیک دی آمید (بیورت) تحت شرایط مایکروویو مورد ارزیابی قرار گرفت. استفاده از روش مایکروویو منجر به استفاده ی بسیار اندک از حلال های آلی، کاهش زمان واکنش و افزایش راندمان محصولات گردید که در جهت توسعه شیمی سبز و حفاظت از محیط زیست محقق شد. همچنین این بیورت ها جهت بررسی فعالیت بازدارندگی بر تکثیر ویروس نقص ایمنی انسانی نوع 1 (HIV-1)، توسط کیت ELISA آنتی ژن p24 HIV-1 مورد ارزیابی قرار گرفته و سه مورد از آن ها (5b، 5c و 5f) فعالیت متوسطی روی ویروس HIV-1 با مقادیر IC50 در محدوده ۱/۵۵ تا ۱۰۰ میکرومولار در مقایسه با آزیدوتیمیدین به عنوان داروی مرجع (۱۱/۰ IC50 = میکرومولار) نشان داد. در نهایت مطالعات داکینگ مولکولی جهت بررسی مکانیسم اثر ترکیبات بر آنزیم پروتئاز ویروس صورت گرفت، که نتایج کارهای عملی آزمایشگاهی و مطالعه داکینگ مولکولی تطابق خوبی را از خود نشان دادند.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Preparation of Imidodicarbonic diamide Derivatives by Microwave Method Using Layered Double Hydroxides (LDHs), as an Efficient Catalyst and Evaluation of their Anti-HIV Effect: Experimental and Theoretical Studies

نویسندگان [English]

  • Zahra Ghiasifar 1
  • Neda Adib pour 2
  • Eskandar Ali pour 1
  • Farzad Kobarfard 3
  • Mohammad Reza Shoushi zadeh 4
1 Department of Organic Chemistry, Islamic Azad University Tehran North Branch, Tehran, Iran
2 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
3 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Marine Pharmaceutical Science Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
چکیده [English]

In this paper, to develop green chemistry, a catalyst based on layered double hydroxides (LDHs) attached by hexamethylene-1,6-diisocyanate (HMDI) and citric acid (LDH-g-HMDI-citric acid) were prepared and characterized by FT-IR, XRD, EDX, SEM, TGA, and DTG analytical methods. The catalytic activity of this recyclable heterogeneous catalyst was evaluated for the synthesis of new imidodicarbonate diamide derivatives (biuret) under microwave conditions. The use of the microwave method led to the use of organic solvents in small amounts, reduced reaction times, and increased yields of products, which was achieved for the development of green chemistry and environmental protection. These biurets were evaluated for inhibitory activity on human immunodeficiency virus type 1 (HIV-1) by HIV-1 p24 antigen ELISA kit and three of them (5b, 5c, and 5f) had moderate activity on HIV -1 virus with IC50 values in the range of 55.1 to 100 μM compared to azidothymidine as the reference drug (IC50 = 0.11 μM). Finally, to investigate the mechanism of the effect of biuret compounds on the virus protease enzyme, docking analysis studies were performed and the results of in vitro test and docking study were in good correlation.

کلیدواژه‌ها [English]

  • Green Chemistry
  • Microwave
  • Layered double hydroxides
  • Imidodicarbonic diamide
  • Anti-AIDS effect
  • Molecular docking

This is an open access article under the CC-BY-SA 4.0 license.( https://creativecommons.org/licenses/by-sa/4.0/)

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