Chalcone organohalogen: thiết kế, tổng hợp, dự đoán ADMET, nghiên cứu động lực học phân tử và hiệu ứng ức chế trên acetylcholinesterase và carbonic anhydrase

Molecular Diversity - Trang 1-17 - 2024
Busra Ozturk Aydin1, Derya Aktas Anil1,2, Yeliz Demir3, Mehmet Abdullah Alagoz4
1Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey
2Department of Chemistry and Chemical Process Technologies, Technical Sciences Vocational School, Ataturk University, Erzurum, Turkey
3Department of Pharmacy Services, Nihat Delibalta Göle Vocational School, Ardahan University, Ardahan, Turkey
4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, Malatya, Turkey

Tóm tắt

Trong nỗ lực khám phá các chất ức chế acetylcholinesterase (AChE) và carbonic anhydrase (CA) tiềm năng, một loạt các dẫn xuất chalcone organohalogen mới (12–20, 23–30) đã được tổng hợp, và cấu trúc hóa học của chúng được xác định bằng phân tích phổ. Chúng thể hiện hiệu ứng ức chế rất mạnh đối với AChE và hCAs (giá trị Ki giao động từ 5.07 ± 0.062 đến 65.53 ± 4.36 nM cho AChE, 13.54 ± 2.55 đến 94.11 ± 10.39 nM cho hCA I, và 5.21 ± 0.54 đến 57.44 ± 3.12 nM cho hCA II). Ngoài ra, các dẫn xuất chalcone với điểm ức chế cao nhất đã được đưa vào vị trí hoạt động của các thụ thể enzym chuyển hóa được chỉ định, và các thuộc tính hấp thụ, chuyển hóa, cũng như độc tính của chúng đã được đánh giá theo ước lượng của ADMET. Các hợp chất 16 và 19 thể hiện điểm ức chế cao nhất, nổi lên như các hợp chất dẫn đầu, và đã truyền cảm hứng cho sự phát triển của các hợp chất mạnh hơn.

Từ khóa

#acetylcholinesterase #carbonic anhydrase #chalcone #organohalogen #ức chế #tổng hợp #dự đoán ADMET #động lực học phân tử

Tài liệu tham khảo

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