Cyclic Benzimidazole Derivatives and Their Antitumor Activity

U posljednjih nekoliko godina interes za proučavanem kemije benzimidazola znatno je porastao zbog njihovog širokog spektra biološkog djelovanja, kao i mnogobrojnih mogućnosti primjene kao materijala u elektronici, u elektrokemiji za zaštitu od korozije, polimera ili optičkih materijala. Struktura benzimidazola sadržana je u vitaminu B12 kao i u strukturi mnogih terapeutskih agensa koji imaju antitumorsko, antiinfektivno, antibakterijsko, antifungalno i mnoga druga biološka djelovanja. Ciklički derivati benzimidazola poput benzimidazo[1,2-a]kinolina, benzimidazo[1,2- -c]kinazolina, benzimidazo[2,1-b]izokinolina kao i mnogi drugi privukli su znatnu pažnju kako organskih sintetskih tako i medicinskih kemičara zbog interesantnih bioloških značajki, ponajprije vrlo dobrog antitumorskog djelovanja. Ciklički derivati benzimidazola imaju planarnu strukturu koja im omogućuje interkaliranje između parova baza dvostruke uzvojnice DNA. Interkalativni način vezivanja danas je jedan od najvažnijih u djelovanju antitumorskih lijekova.Over the past years benzimidazole derivatives are one of the most extensively studied classes of heterocyclic compounds, and have received much attention from synthetic organic as well as medicinal chemists, because of their well known biological activities and their applications in several areas as materials in electronics, in electrochemistry as anticorrosive agents, as polymers or optical materials and fluorescent tags in DNA sequencing. The structure of vitamin B12, as an example, contains a benzimidazole group. Compounds containing benzimidazole nuclei show anticancer, antineoplastic, antiinfective, antibacterial, antifungal and many others activities. Due to the structural similarity of benzimidazole nuclei with some naturally occurring compounds such as purine, they can easily interact with biomolecules of the living systems. The introduction of an additional substituent on the benzimidazole nuclei has been increasing attention in the expectation that such changes could potentially affect the interaction of the molecules with biological targets. Fused cyclic benzimidazole derivatives, as benzimidazo[1,2-a]quinolines,benzimidazo[1,2-c]quinazolines, benzimidazo[2,1-b]isoquinolines and many others, have also interesting biological activities and most of them are very good anticancer agents. DNA is the molecular target of many anticancer drugs in clinical use and development. Compounds which can bind to DNA with intercalative or non-intercalative mechanism play a major role in biological processes such as gene transcription or DNA replication. Benzoannulated benzimidazole analogues contain a planar chromophore and have the ability to become inserted between adjacent base pairs of DNA double helix. Intercalators are recognized as one of the most important classes of anticancer agents. So an understanding of the drug-DNA interactions is a promising approach to developing novel reagents and plays a key role in pharmacology today

Cyclic Benzimidazole Derivatives and Their Antitumor Activity

U posljednjih nekoliko godina interes za proučavanem kemije benzimidazola znatno je porastao zbog njihovog širokog spektra biološkog djelovanja, kao i mnogobrojnih mogućnosti primjene kao materijala u elektronici, u elektrokemiji za zaštitu od korozije, polimera ili optičkih materijala. Struktura benzimidazola sadržana je u vitaminu B12 kao i u strukturi mnogih terapeutskih agensa koji imaju antitumorsko, antiinfektivno, antibakterijsko, antifungalno i mnoga druga biološka djelovanja. Ciklički derivati benzimidazola poput benzimidazo[1,2-a]kinolina, benzimidazo[1,2- -c]kinazolina, benzimidazo[2,1-b]izokinolina kao i mnogi drugi privukli su znatnu pažnju kako organskih sintetskih tako i medicinskih kemičara zbog interesantnih bioloških značajki, ponajprije vrlo dobrog antitumorskog djelovanja. Ciklički derivati benzimidazola imaju planarnu strukturu koja im omogućuje interkaliranje između parova baza dvostruke uzvojnice DNA. Interkalativni način vezivanja danas je jedan od najvažnijih u djelovanju antitumorskih lijekova.Over the past years benzimidazole derivatives are one of the most extensively studied classes of heterocyclic compounds, and have received much attention from synthetic organic as well as medicinal chemists, because of their well known biological activities and their applications in several areas as materials in electronics, in electrochemistry as anticorrosive agents, as polymers or optical materials and fluorescent tags in DNA sequencing. The structure of vitamin B12, as an example, contains a benzimidazole group. Compounds containing benzimidazole nuclei show anticancer, antineoplastic, antiinfective, antibacterial, antifungal and many others activities. Due to the structural similarity of benzimidazole nuclei with some naturally occurring compounds such as purine, they can easily interact with biomolecules of the living systems. The introduction of an additional substituent on the benzimidazole nuclei has been increasing attention in the expectation that such changes could potentially affect the interaction of the molecules with biological targets. Fused cyclic benzimidazole derivatives, as benzimidazo[1,2-a]quinolines,benzimidazo[1,2-c]quinazolines, benzimidazo[2,1-b]isoquinolines and many others, have also interesting biological activities and most of them are very good anticancer agents. DNA is the molecular target of many anticancer drugs in clinical use and development. Compounds which can bind to DNA with intercalative or non-intercalative mechanism play a major role in biological processes such as gene transcription or DNA replication. Benzoannulated benzimidazole analogues contain a planar chromophore and have the ability to become inserted between adjacent base pairs of DNA double helix. Intercalators are recognized as one of the most important classes of anticancer agents. So an understanding of the drug-DNA interactions is a promising approach to developing novel reagents and plays a key role in pharmacology today

Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives

Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 μM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11

Sinteza i biološko vrednovanje novih derivata 2-fenil-benzimidazol-1-acetamida kao potencijalnih anthelmintika

The present study describes synthesis of a series of 2-phenyl benzimidazole-1-acetamide derivatives and their evaluation for anthelmintic activity using Indian adult earthworms, Pheretima posthuma. The structure of the title compounds was elucidated by elemental analysis and spectral data. The compounds 4-({[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]acetyl}amino) benzoic acid (3a), N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-benzyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3d), N-(4-hydroxyphenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3f), 2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3h), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N\u27-phenylacetohydrazide (3k), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-(4-nitrophenyl) acetamide (3n) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3q) were better to paralyze worms whereas N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-(4-nitrophenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1yl] acetamide (3e), 4-({[2-(4-chlorophenyl)-1H-benzimidazol-1-yl] acetyl} amino) benzoic acid (3j), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-ethylacetamide (3l) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3q) were better to cause death of worms compared to the anthelmintic drug albendazole.U radu je opisana sinteza derivata 2-fenil-benzimidazol-1-acetamida i ispitivanje njihovog anthelmintičkog djelovanja na odrasle indijske gliste, Pheretima posthuma. Struktura sintetiziranih spojeva određena je elementarnom analizom i spektroskopskim metodama. Spojevi 4-({[2-(4-nitrofenil)-1H-benzimidazol-1-il]acetil}amino) benzojeva kiselina (3a), N-etil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3c), N-benzil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3d), N-(4-hidroksifenil)-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3f), 2-[2-(4-nitrofenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3h), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N\u27-fenilacetohidrazid (3k), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-(4-nitrofenil) acetamid (3n) i 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3q) jače paraliziraju gliste, a N-etil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3c), 2-[2-(4-nitrofenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3h), 4-({[2-(4-klorfenil)-1H-benzimidazol-1-il]acetil}amino) benzojeva kiselina (3j), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-etilacetamid (3l) i 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3q) učinkovitije usmrćuju gliste nego anthelmintik albendazol