RESUMO
Human kinesin Eg5 is a potential inhibiting site for cancer chemotherapy. Blocking metaphase by binding foreign inhibitors with Eg5 eventually leads to apoptotic cell death. Here, we report the pyrazolopyrimidine derivates as potent inhibitors of Eg5 that prevents mitotic kinesin progression. IC50 values were evaluated against the motor domain of Eg5 using steady-state ATPase assay. To better understanding, we have performed molecular docking simulation. It reveals that the interactions of the proposed inhibitors with both the allosteric sites (helices α2, α3 and loopL5, and helices α4 & α6). Out of fifteen pyrazolopyrimidine derivates, three compounds (12, 25, and 27) have shown significant inhibition of Eg5. The synthesized compounds (12, 25, and 27) were tested for their in-vitro anticancer activity against cervical cancer cell line (HeLa).
Assuntos
Antineoplásicos/química , Cinesinas/antagonistas & inibidores , Pirazóis/química , Pirimidinas/química , Sítio Alostérico , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Células HeLa , Humanos , Cinesinas/metabolismo , Simulação de Acoplamento Molecular , Pirimidinas/metabolismo , Pirimidinas/farmacologia , Relação Estrutura-AtividadeRESUMO
The basis of the present study was to distinguish the existence of any genetic variability among populations of Culex quinquefasciatus which would be a valuable tool in the management of mosquito control programmes. In the present study, population of Cx. quinquefasciatus collected at different locations in Tamil Nadu were analyzed for their genetic variation based on 28S rDNA D2 region nucleotide sequences. A high degree of genetic polymorphism was detected in the sequences of D2 region of 28S rDNA on the predicted secondary structures in spite of high nucleotide sequence similarity. The findings based on secondary structure using rDNA sequences suggested the existence of a complex genotypic diversity of Cx. quinquefasciatus population collected at different locations of Tamil Nadu, India. This complexity in genetic diversity in a single mosquito population collected at different locations is considered an important issue towards their influence and nature of vector potential of these mosquitoes.
Assuntos
Culex/classificação , Culex/genética , Variação Genética , Filogeografia , Animais , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Índia , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA Ribossômico 28S/genética , Análise de Sequência de DNARESUMO
The basis of the present study was to distinguish the existence of any genetic variability among populations of Culex quinquefasciatus which would be a valuable tool in the management of mosquito control programmes. In the present study, population of Cx. quinquefasciatus collected at different locations in Tamil Nadu were analyzed for their genetic variation based on 28S rDNA D2 region nucleotide sequences. A high degree of genetic polymorphism was detected in the sequences of D2 region of 28S rDNA on the predicted secondary structures in spite of high nucleotide sequence similarity. The findings based on secondary structure using rDNA sequences suggested the existence of a complex genotypic diversity of Cx. quinquefasciatus population collected at different locations of Tamil Nadu, India. This complexity in genetic diversity in a single mosquito population collected at different locations is considered an important issue towards their influence and nature of vector potential of these mosquitoes.
RESUMO
The ectoparasitic tick, Rhipicephalus (Boophilus) microplus collected at various cattle farms in and around Chennai was subjected to treatment of different crude solvent extracts of leaves of Ocimum basilicum and Spilanthes acmella for acaricidal activity. Among various solvent extracts of leaves of O. basilicum and S. acmella used, chloroform extract of O. basilicum at concentrations between 6% and 10% exhibited 70% and 100% mortality of ticks when compared to control. The LC50 and LC90 values of the chloroform extract of leaves of O. basilicum treatment on the ticks after 24 h were observed as 5.46% and 7.69%. Quantitative and qualitative analysis of α- and ß- carboxylesterase enzymes in the whole gut homogenate of cattle tick, R. microplus treated with chloroform extract of leaves of O. basilicum revealed higher level of activities for the enzymes. This indicated that there was an induced response in the tick, R. microplus against the toxic effects of the extract of O. basilicum.
