| Journal: | Brazilian journal of pharmaceutical sciences |
| Database: | PERIÓDICA |
| System number: | 000396325 |
| ISSN: | 1984-8250 |
| Authors: | Rubab, Kaniz1 Abbasi, Muhammad Athar1 Aziz-ur-Rehman1 Siddiqui, Sabahat Zahra1 Ashraf, Muhammad2 Shaukat, Ayesha2 Ahmad, Irshad3 Lodhi, Muhammad Arif4 Khan, Farman Ali4 Shahid, Muhammad5 Akhtar, Muhammad Nadeem6 |
| Institutions: | 1Government College University, Department of Chemistry, Lahore, Punjab. Pakistán 2Government College University, Department of Biochemistry and Biotechnology, Lahore, Punjab. Pakistán 3The Islamia University of Bahawalpur, Department of Pharmacy, Bahawalpur, Punjab. Pakistán 4Abdul Wali Khan University, Department of Biochemistry, Mardan, Jaiber Pajtunjuá. Pakistán 5University of Agriculture, Department of Biochemistry, Faisalabad. Pakistán 6University Malaysia Pahang, Faculty of Industrial Sciences & Technology, Kuantan Pahang. Malasia |
| Year: | 2015 |
| Season: | Oct-Dic |
| Volumen: | 51 |
| Number: | 4 |
| Pages: | 931-947 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents |
| Portuguese abstract | Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados |
| Disciplines: | Química |
| Keyword: | Química farmacéutica, Acetamida, Síntesis química, Actividad antibacteriana, Inhibición enzimática, Actividad hemolítica |
| Keyword: | Chemistry, Medicinal chemistry, Acetamide, Chemical synthesis, Antibacterial activity, Enzymatic inhibition, Hemolytic activity |
| Full text: | Texto completo (Ver HTML) |
