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Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents.

Ravula P, Vamaraju HB, Paturi M, Chandra Jn NS, Kolli S - EXCLI J (2016)

Bottom Line: Results of in vivo anticancer activity revealed that compound 5c showed the highest percentage increase in life span ( %ILS), and mean survival time (MST) with 75.13 % and 32.4 ± 0.53 days respectively.In silico prediction of toxicities, and drug score profiles of designed compounds are promising.A correlation made between the results obtained by antiproliferative study and molecular docking studies suggest that the synthesized compounds may be beneficial as molecular scaffolds for antiproliferative activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Guru Nanak Institutions Technical Campus, School of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad- 501301, India.

ABSTRACT
A new series of pyrazole derivatives were designed by docking into vascular endothelial growth factor receptor-2 (VEGFR-2) kinase active site. The designed compounds were synthesized and evaluated for in vitro antiproliferative activity against HT-29 colon and PC-3 prostate cancer cell lines, and angioinhibitory activity in chorioallantoic membrane (CAM) model. Based on the obtained antiproliferative activity results of in vitro and CAM assay, compounds 4b, 4c, 4f, 5b, 5c and 5f were selected, and tested for anticancer activity using in vivo ehrlich ascites carcinoma (EAC) bearing mice. Compound 5c showed the highest in vitro antiproliferative activity against HT-29 and PC-3 with IC50 values of 6.43 µM and 9.83 µM respectively and comparable to reference drug Doxorubicin. Results of in vivo anticancer activity revealed that compound 5c showed the highest percentage increase in life span ( %ILS), and mean survival time (MST) with 75.13 % and 32.4 ± 0.53 days respectively. Moreover, compound 5c demonstrated significant reduction of microvessel density (MVD) in CAM assay. In silico prediction of toxicities, and drug score profiles of designed compounds are promising. A correlation made between the results obtained by antiproliferative study and molecular docking studies suggest that the synthesized compounds may be beneficial as molecular scaffolds for antiproliferative activity.

No MeSH data available.


Related in: MedlinePlus

In vitro antiproliferative activity of synthesized compounds against two cell lines
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T1: In vitro antiproliferative activity of synthesized compounds against two cell lines

Mentions: Antiproliferative screening of the synthesized compounds 4a-4g and 5a-5g was carried out by in vitro method using MTT assay against two cell lines namely HT-29 (colon) and PC-3 (prostate). Doxorubicin was used as reference drug. From percentage inhibition IC50 values were calculated in µM and shown in Table 1(Tab. 1). Overall, better antiproliferative activity was observed for 5a-5g series as compared to 4a-4g series against two cell lines. Particularly, compounds possessing chloro and methoxy substitutions on phenyl ring at para position (5c and 5f) showed highest antiproliferative activity against HT-29 and PC-3 cell lines with IC50 values ranging from 6.43 µM to 10.15 µM as compared to corresponding ortho substituted compounds (5b and 5e). However, compounds with methyl substitution at para position (4d and 5d), compounds 4a and 5a, and napthyl derivatives (4g and 5g) exhibited less antiproliferative activity.


Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents.

Ravula P, Vamaraju HB, Paturi M, Chandra Jn NS, Kolli S - EXCLI J (2016)

In vitro antiproliferative activity of synthesized compounds against two cell lines
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834670&req=5

T1: In vitro antiproliferative activity of synthesized compounds against two cell lines
Mentions: Antiproliferative screening of the synthesized compounds 4a-4g and 5a-5g was carried out by in vitro method using MTT assay against two cell lines namely HT-29 (colon) and PC-3 (prostate). Doxorubicin was used as reference drug. From percentage inhibition IC50 values were calculated in µM and shown in Table 1(Tab. 1). Overall, better antiproliferative activity was observed for 5a-5g series as compared to 4a-4g series against two cell lines. Particularly, compounds possessing chloro and methoxy substitutions on phenyl ring at para position (5c and 5f) showed highest antiproliferative activity against HT-29 and PC-3 cell lines with IC50 values ranging from 6.43 µM to 10.15 µM as compared to corresponding ortho substituted compounds (5b and 5e). However, compounds with methyl substitution at para position (4d and 5d), compounds 4a and 5a, and napthyl derivatives (4g and 5g) exhibited less antiproliferative activity.

Bottom Line: Results of in vivo anticancer activity revealed that compound 5c showed the highest percentage increase in life span ( %ILS), and mean survival time (MST) with 75.13 % and 32.4 ± 0.53 days respectively.In silico prediction of toxicities, and drug score profiles of designed compounds are promising.A correlation made between the results obtained by antiproliferative study and molecular docking studies suggest that the synthesized compounds may be beneficial as molecular scaffolds for antiproliferative activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Guru Nanak Institutions Technical Campus, School of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad- 501301, India.

ABSTRACT
A new series of pyrazole derivatives were designed by docking into vascular endothelial growth factor receptor-2 (VEGFR-2) kinase active site. The designed compounds were synthesized and evaluated for in vitro antiproliferative activity against HT-29 colon and PC-3 prostate cancer cell lines, and angioinhibitory activity in chorioallantoic membrane (CAM) model. Based on the obtained antiproliferative activity results of in vitro and CAM assay, compounds 4b, 4c, 4f, 5b, 5c and 5f were selected, and tested for anticancer activity using in vivo ehrlich ascites carcinoma (EAC) bearing mice. Compound 5c showed the highest in vitro antiproliferative activity against HT-29 and PC-3 with IC50 values of 6.43 µM and 9.83 µM respectively and comparable to reference drug Doxorubicin. Results of in vivo anticancer activity revealed that compound 5c showed the highest percentage increase in life span ( %ILS), and mean survival time (MST) with 75.13 % and 32.4 ± 0.53 days respectively. Moreover, compound 5c demonstrated significant reduction of microvessel density (MVD) in CAM assay. In silico prediction of toxicities, and drug score profiles of designed compounds are promising. A correlation made between the results obtained by antiproliferative study and molecular docking studies suggest that the synthesized compounds may be beneficial as molecular scaffolds for antiproliferative activity.

No MeSH data available.


Related in: MedlinePlus