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A study of tetrazole derivatives was found to have the following inhibitory acti

ID: 924852 • Letter: A

Question

A study of tetrazole derivatives was found to have the following inhibitory activity at an esterase enzyme.

a) Predict the IC50 value for the cyano group (X = CN, ? = +0.66).

b) Based upon the SAR data above explain the probable effect of the substituents on the inhibitor/enzyme interactions.

c) Explainwhythemethoxyanalogue(X=OCH3,?=-0.267)wouldprobably not be worth synthesizing and screening.

d) The tert-butyl analogue (X = C(CH3)3, ? = -0.197) exhibited an IC50 value of 5,000 nM. Is the activity of the analogue consistent with the data above? Explain why or why not.

A study of tetrazole derivatives was found to have the following inhibitory activity at an esterase enzyme. A Hansch equation for the activity listed above was determined to be: Log 1/C = 2.04 sigma + 6.7 n = 5, r^2 = 0.993 Predict the IC_50 value for the cyano group (X = CN, sigma = +0.66). Based upon the SAR data above explain the probable effect of the substituents on the inhibitor/enzyme interactions. Explain why the methoxy analogue (X = OCH_3, sigma = -0.267) would probably not be worth synthesizing and screening. The tert-butyl analogue (X = C(CH_3)_3, sigma = -0.197) exhibited an IC_50 value of 5, 000 nM. Is the activity of the analogue consistent with the data above? Explain why or why not.

Explanation / Answer

a) the relation is

log 1/C = 2.04 + 6.7

IC50 value for CN will be

log 1/C = 2.04 X 0.66 + 6.7 = 8.046

So C = 111173172.7 = 1.11 X 10^8

b) as per the study the MIC when NO2 group is present is minimum which shows that it is best substituent to increse the acitivity of the compound

While presence of CN group will decrease the activity drastically

c) Let us calcualte IC50 for Methoxy group

log 1/C = 2.04 + 6.7

log 1/C = 2.04 (-0.267) + 6.7 = 6.155

C = 1.42 X 10^6 nM

so it is very high.

Which means we need high concentration of compound when the substiutent is methoxy group.

d) log 1/C = 2.04 + 6.7

C = 1.94 X 10^6

so it is not consistent with the data above