The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
Synthesis
of 50 analogues of the natural insecticide synergists,
dillapiol and sesamol, is reported. These were evaluated as potential
insecticide synergists based on their inhibition of human CYP3A4.
The most potent inhibitors have a relatively large hydrophobic substituent
at either position 5 or 6 of these molecules. For example, 5-(benzyloxy)-6-(3-phenylsulfonyl)propyl)benzo[
d
][1,3]dioxole (
18
) and the diphenyl acetate
of (6,7-dimethoxybenzo[
d
][1,3]dioxol-5-yl)propan-1-ol
(
5n
) show inhibitory concentrations for 50% activity
IC
50
values of 0.086 and 0.2 μM, respectively. These
compounds are 106 and 46 times more potent than dillapiol whose IC
50
for the inhibition of CYP3A4 is 9.2 μM. The
ortho
-chloro analogue (
8f
), whose activity
is 86 times the activity of dillapiol, is the most potent of the fourteen
5-(benzyloxy-6-(2 propenyl)benzo[
d
][1,3]dioxoles
prepared for this study.
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