Synthesis and anticancer activity of ethyl 5‐amino‐1‐N‐substituted‐imidazole‐4‐carboxylate building blocks

Abstract

A series of 5‐amino‐1‐N‐substituted‐imidazole‐4‐carboxylate building blocks was synthesized and assayed for their antiproliferative potential against human cancer cell lines, including HeLa (cervical), HT‐29, HCT‐15 (colon), A549 (lung), and MDA‐MB‐231 (breast) cells. The preliminary screening results revealed that several derivatives containing alkyl chains at the N‐1 position of the imidazole core demonstrate a certain inhibitory effect on growth and proliferation. A significant effect was observed following ethyl 5‐amino‐1‐dodecyl‐1H‐imidazole‐4‐carboxylate (5e) treatment for 72 h. The IC50 value for HeLa cells was 0.737 ± 0.05 μM, whereas that for HT‐29 cells was 1.194 ± 0.02 μM. Further investigations revealed that 5e significantly inhibited tumor cell colony formation and migration, and it exhibited antiadhesive effects on HeLa cells as well as antitubulin activity along with the induction of early apoptosis of HeLa and HT‐29 cells. In addition, derivative 5e significantly reduced the cell mitochondrial membrane potential in a dose‐dependent manner and induced early apoptosis of HeLa and HT‐29 cells, indicating that 5e may serve as a lead compound for further drug discovery and development.

Xinazolin Alkaloidlarining Tiofenli Analoglari: 2-N(alkil, Aril)-Tieno[2,3-D]pirimidinonlarning Sintezi Va Modifikasiyasi

“…In recent years, much information has been published about pyrimidine derivatives condensed with various heterocycles [12], such as: purines, pteridines, quinazolines, pyridopyrimidines, pyrimidoazepines, furo-and pyrrolopyrimidines, thienopyrimidines, their synthesis and chemical transformations. also confirm the importance of these class combinations [13][14][15][16]3,[17][18][19][20][21][22].…”

“…The corresponding 3,1-oxazine-4-one (18) was obtained by its interaction with acetic anhydride and the 2-chloromethyl derivative ( 19) by its interaction with chloroacetyl chloride in the presence of triethylamine. The resulting 3,1-oxazine-4-ones (18,19) react with panisidine in a 1:1 and 1:2 ratio to give thieno [2,3-d]pyrimidine (20,21) containing alkyl and aryl groups in the expected 2 -and 3-positions: The corresponding thienopyrimidin-4-ones (23) were obtained by acylation and heating in acidic medium of the amino group in nitriles of 2-aminothiophene-3-carboxylic acid (22) containing various substituents in the 4,5-state [33]. 4-Iminothieno[2,3-d]-3,1-oxazines formed as intermediates in the reaction are redistributed into thienopyrimidine-4-ones (23).…”

“…Kondensirlangan pirimidinlarning kimyosi va amaliy ahamiyati, jumladan keng ko'lamli biologik faolligi turli davlatlarning olimlari e'tiborini tortib kelmoqda [11]. So'nggi yillarda pirimidin xalqasining turli geteroxalqalar bilan kondensirlangan hosilalari [12], masalan: purinlar, pteridinlar, xinazolinlar, piridopirimidinlar, pirimidoazepinlar, furo-va pirrolopirimidinlar, tiyenopirimidinlar, ularning sintezi va kimyoviy o'zgarishlari haqida keng ko'lamda chop etilayotgan ma'lumotlar ham bu sinf birikmalarining muhimligini tasdiqlaydi [13][14][15][16]3,[17][18][19][20][21][22].…”

“…В последние годы опубликовано большое количество информации о производных пиримидина, конденсированных с различными гетероциклами [12], таких как: пурины, птеридины, хиназолины, пиридопиримидины, пиримидоазепины, фуро-и пирролопиримидины, тиенопиримидины, их синтезе и химических превращениях. также подтверждают важность этих комбинаций классов [13][14][15][16]3,[17][18][19][20][21][22].…”

Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective

“…Compound 44 showed the best anticancer activity with HeLa, HT-29, A549, HCT-15, and MDA-MB-231 cell lines with IC 50 values of 0.81, 1.77, 15.22, 17.92, and 5.48 μM. Reference drug Doxorubicin presented IC 50 values of 0.1, 0.03, 1.1, 0.27, and 0.51 Μm, respectively [ 161 ]. Singh et al (2021) synthesized and reported C 6 -substituted benz[4,5]imidazo[1,2-α]quinoxaline derivatives and performed their anticancer evaluation.…”