Heba A Ibrahim1, Fadi M Awadallah2, Hanan M Refaat1, Kamilia M Amin2. 1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University In Egypt, Cairo, Egypt. 2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, 11562 Cairo, Egypt.
Abstract
AIM: Computer-aided drug design techniques were adopted to design three series of 2-substituted-5-nitrobenzimidazole derivatives hybridized with piperzine 5a,b, oxadiazole 7a,b, 9, 14a-c and triazolo-thiadiazole moieties 12a-d, as VEGFR-2/c-Met kinase inhibitors. MATERIALS & METHODS: The designed compounds were synthesized adopting the chemical pathways outlined in schemes 1 and 2 to afford the desired three series followed by evaluating their inhibitory activities against VEGFR-2 and c-Met and in vitro anticancer activities. RESULT: Analogs bearing substituted phenyl ring attached to oxadiazole ring 14a showed the greatest inhibitory activities against non-small-cell lung cancer NCI-H522 and melanoma SK-MEL-2 with inhibition percent of 48.70 and 42.62, respectively. Moreover, unsubstituted phenoxymethyl derivative 12d exhibited promising inhibitory activity against VEGFR-2 and c-Met (35.88 and 88.48%), respectively. CONCLUSION: The above results revealed that 2-substituted-5-nitrobenzimidazole hybridized with various heterocyclic scaffolds could be a potential anticancer agent.
AIM: Computer-aided drug design techniques were adopted to design three series of 2-substituted-5-nitrobenzimidazole derivatives hybridized with piperzine 5a,b, oxadiazole 7a,b, 9, 14a-c and triazolo-thiadiazole moieties 12a-d, as VEGFR-2/c-Met kinase inhibitors. MATERIALS & METHODS: The designed compounds were synthesized adopting the chemical pathways outlined in schemes 1 and 2 to afford the desired three series followed by evaluating their inhibitory activities against VEGFR-2 and c-Met and in vitro anticancer activities. RESULT: Analogs bearing substituted phenyl ring attached to oxadiazole ring 14a showed the greatest inhibitory activities against non-small-cell lung cancer NCI-H522 and melanoma SK-MEL-2 with inhibition percent of 48.70 and 42.62, respectively. Moreover, unsubstituted phenoxymethyl derivative 12d exhibited promising inhibitory activity against VEGFR-2 and c-Met (35.88 and 88.48%), respectively. CONCLUSION: The above results revealed that 2-substituted-5-nitrobenzimidazole hybridized with various heterocyclic scaffolds could be a potential anticancer agent.
Entities:
Keywords:
computational chemistry; drug design; drug development; molecular modeling