Screen Against Gram Negative Bacteria?

[mattodd]

Paul Hergenrother gave a really nice talk at the recent SCI antimicrobials meeting. His subject was the prediction of structures of small molecules able to accumulate inside gram negative bacteria, i.e. able to penetrate and then stay in. What modifications can be made that turn compounds from effective vs gram+ to gram- ?

To paraphrase, they empirically found that positively charged compounds, particularly primary amines, tend to accumulate, but there was also a dependence on "globularity" with low-globularity (i.e. "flat") compounds accumulating well. Rules for effective accumulation have been grouped together in a tool (www.entry-way.org) to which one can submit a bunch of SMILES to determine if any of the compounds are predicted to accumulate. One would eventually want to see if any of those compounds actually kill gram -ve bacteria, but at least this is a useful triage, getting around the efflux problem.

What I'd like to do is: 1) Submit all our OSM compound strings to the tool (www.entry-way.org) to see if we're already sitting on compounds predicted to accumulate. 2) If we are, let's get them physically tested to check they actually do accumulate: Paul indicated to me he's happy to test any such OSM compounds in his lab, which is great. 3) If they are indeed accumulators, we should finally send for bio evaluation vs. gram neg. CO-ADD evaluate vs. several, which would be the natural place to send.

So, we need: a volunteer to batch submit the OSM compounds through the website and report back here any compounds predicted to be accumulators.

Timeline: An email from CO-ADD 6 days ago said that the last day to ship was 7th December. I'll clarify if that's the last day for them to receive compounds.

@maratsydney this is the thing I mentioned. Let's group your compounds (everyone else FYI: these are examples of 5- and 8-substituted Series 4 compounds to see if there is a biological difference) with any that come out of this exercise and ship by the 7th, OK?

(One may also want to consider other groups that might achieve the same thing such as N-alkyl pyridiniums, amidines, guanidines, but let's not get ahead of ourselves)

Obviously this has partial relevance to #576 in terms of possible other areas we can apply ourselves.

Further Reading: 2018 review on gram -ve accumulation.

2018 Review on Accumulation Assays.

[drc007]

@mattodd links to website are broken

[mattodd]

Thanks. Fixed. Odd.

[MFernflower]

Compounds that score well from Marat's Suzuki coupling work: @mattodd MK063 MK081 MK041 MK066 MK091 MK079 MK064

[drc007]

Read the paper but can't work out what is a good "score"?

[MFernflower]

I used the web interface and considered those with at-least two green marks as a passable score @drc007 @mattodd

[mattodd]

Did the primary amine-containing compounds MMV671651 or MMV688899 not come up? https://github.com/OpenSourceMalaria/Series4/wiki/Pyrazine-Side-Chain-Modifications---Ethers

[MFernflower]

Please note that I was hand screening marat's Suzuki library and nothing else @mattodd

[mattodd]

Ah - I'd thought it was possible to submit a batch. Not?

[MFernflower]

Well openbabelgui would overflow when i'd attempt to manipulate the master list so i figured that screening something was better than nothing @mattodd

[mattodd]

@MFernflower what's the input format(s) accepted? I'd thought a csv of SMILEs, but I've not created an account to see.

@maratsydney COADD have confirmed they need to receive compounds by Dec 7th. Definitely plan to get yours in by that date, and let's see what the analysis here throws up in the meantime. We can include any candidates that seem promising from the in silico accumulation analysis.

[MFernflower]

@mattodd the format is described as follows

"Lists of SMILES strings can be constructed with a text editor or Excel. Each line represents a molecule. The first column contains SMILES strings and the second column contains the molecule name. Columns are separated by any whitespace. Acceptable file extensions are .smi and .txt"

[maratsydney]

I played with it for a while and managed to submit as a batch all Series 4 compounds, but for some reason it made 5 copies of each entry (pdf and csv reports can be found here.

In short most of the compounds hit 2 out of 3 criteria (low flexibility and low globularity). Third criteria require to have primary amino group, and we have relatively few compounds that will meet all three criteria, I guess it would be logical to send them for assay. Minor problem that I notice, as per picture above posted by @MFernflower, this software doesn't recognize amino group directly attached to aryl(See structures attached below). I am not sure if it's meant to be this way or it is just some problems of software interpretation (didn't find anything specific about the placement of amino group apart from statement that it should be sterically accessible) .

[MFernflower]

I think it would a good idea to check if any interesting compounds are sitting in the fridge that you might have made prior as our ship out deadline is probably only December 4th (as per tweet stating compounds must be received by dec 7) - would def send off the aniline compounds, the indole hit and whatever things on hand that contain a free amino group @maratsydney

Shame the software seems so buggy hopefully they will improve upon it

[drc007]

I suspect that a basic amine is required that will be positively charged at physiological pH. An amino group attached to an aromatic ring is an aniline, and is non-basic. It would not be charged at physiological pH. Reading the paper this does appear to be a key requirement.

[mattodd]

Agreed @drc007 - I suspect they're wise to aliphatic vs aromatic differences.

So @maratsydney @edwintse - which of the compounds in Marat's search above have primary amines (or at least hit all 3 criteria) that we actually have samples for? Needn't be them all, but if we have such things, let's send them to CO-ADD by the deadline. We would separately send the same compounds to Paul for assaying. I'll clarify how much is needed.

[maratsydney]

My bad, completely missed that point that it should be charged and aniline type of amino group is way less basic. Unfortunately, we have only few aliphatic primary amines in our library as OSM-538 shown below (my guess it is located now in London with @edwintse ) and they fail to comply flexibility criteria.

So even though aniline type amines predict to work not as good against gram-negative bacteria it is still worth to test it at CO-ADD facility since they perform range of assays. Below list of compounds that I will be sending for evaluation tomorrow, if you have any other suggestions about which samples should be sent let me know. Compounds to send to CO-AAD.zip

---

---

Internal ID	SMILES	InChI	CnChI Key
MK113-1a	C12=NN=C(C3=CC=CC=C3)N1C(OCCC4=CC=CC=C4)=CN=C2	"InChI=1S/C19H16N4O/c1-3-7-15(8-4-1)11-12-24-18-14-20-13-17-21-22-19(23(17)18)16-9-5-2-6-10-16/h1-10,13-14H,11-12H2"	YRTHPBSIEMFKFB-UHFFFAOYSA-N
MK126-1b	COC(C=C1)=CC=C1C2=NN=C3C(OCCC4=CC=CC=C4)=NC=CN32	"InChI=1S/C20H18N4O2/c1-25-17-9-7-16(8-10-17)18-22-23-19-20(21-12-13-24(18)19)26-14-11-15-5-3-2-4-6-15/h2-10,12-13H,11,14H2,1H3"	KNDAUWHMGBUKCB-UHFFFAOYSA-N
MK114-1a	COC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC=C4)N32	"InChI=1S/C20H18N4O2/c1-25-17-9-7-16(8-10-17)20-23-22-18-13-21-14-19(24(18)20)26-12-11-15-5-3-2-4-6-15/h2-10,13-14H,11-12H2,1H3"	FOEYJDQRLPZFOG-UHFFFAOYSA-N
MK121-1b	COC(C=C1)=CC=C1C2=NN=C3C(SCCC4=CC=CC=C4)=NC=CN32	"InChI=1S/C20H18N4OS/c1-25-17-9-7-16(8-10-17)18-22-23-19-20(21-12-13-24(18)19)26-14-11-15-5-3-2-4-6-15/h2-10,12-13H,11,14H2,1H3"	GEUZYLOQEWPPTC-UHFFFAOYSA-N
MK127-1a	COC(C=C1)=CC=C1C2=NN=C3C=NC=C(SCCC4=CC=CC=C4)N32	"InChI=1S/C20H18N4OS/c1-25-17-9-7-16(8-10-17)20-23-22-18-13-21-14-19(24(18)20)26-12-11-15-5-3-2-4-6-15/h2-10,13-14H,11-12H2,1H3"	XKLPATLXLSUHOI-UHFFFAOYSA-N
MK096-1	C12=NN=CN1C(OCCC3=CC=CC=C3)=CN=C2	"InChI=1S/C13H12N4O/c1-2-4-11(5-3-1)6-9-18-13-12-16-15-10-17(12)8-7-14-13/h1-5,7-8,10H,6,9H2"	OVMOYCYDOGFLPO-UHFFFAOYSA-N
MK086-1	C12=NN=CN1C(SCCC3=CC=CC=C3)=CN=C2	"InChI=1S/C13H12N4S/c1-2-4-11(5-3-1)6-7-18-13-9-14-8-12-16-15-10-17(12)13/h1-5,8-10H,6-7H2"	SFKFITTZRQEVSE-UHFFFAOYSA-N
MK105-2	C1(NCCC2=CC=CC=C2)=NC=CN3C1=NN=C3	"InChI=1S/C13H13N5/c1-2-4-11(5-3-1)6-7-14-12-13-17-16-10-18(13)9-8-15-12/h1-5,8-10H,6-7H2,(H,14,15)"	ZKSCHIOOMCSXEE-UHFFFAOYSA-N
MK006-3	C12=NN=CN1C(OCCC3=CC=CC=C3)=CN=C2	"InChI=1S/C13H12N4O/c1-2-4-11(5-3-1)6-7-18-13-9-14-8-12-16-15-10-17(12)13/h1-5,8-10H,6-7H2"	VFFDMAJXCFVHJC-UHFFFAOYSA-N
MK035-1	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C5C(NC=C5)=C4)N32)=CC=C1F	"InChI=1S/C21H15F2N5O/c22-16-4-1-13(9-17(16)23)6-8-29-20-12-24-11-19-26-27-21(28(19)20)15-3-2-14-5-7-25-18(14)10-15/h1-5,7,9-12,25H,6,8H2"	VHFREJHLTSVZGA-UHFFFAOYSA-N
MK065-1	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(Cl)C(N)=C4)N32)=CC=C1F	"InChI=1S/C19H14ClF2N5O/c20-13-3-2-12(8-16(13)23)19-26-25-17-9-24-10-18(27(17)19)28-6-5-11-1-4-14(21)15(22)7-11/h1-4,7-10H,5-6,23H2"	UUAZLIWHOSTWRP-UHFFFAOYSA-N
MK067-1	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=CC(N)=C4)N32)=CC=C1F	"InChI=1S/C19H15F2N5O/c20-15-5-4-12(8-16(15)21)6-7-27-18-11-23-10-17-24-25-19(26(17)18)13-2-1-3-14(22)9-13/h1-5,8-11H,6-7,22H2"	CQZOPOXKTPBXOH-UHFFFAOYSA-N
MK041-1	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(N)C=C4)N32)=CC=C1F	"InChI=1S/C19H15F2N5O/c20-15-6-1-12(9-16(15)21)7-8-27-18-11-23-10-17-24-25-19(26(17)18)13-2-4-14(22)5-3-13/h1-6,9-11H,7-8,22H2"	PGJZGRJIPPSPJV-UHFFFAOYSA-N
MK094-1	C1(SCCC2=CC=CC=C2)=NC=CN3C1=NN=C3	"InChI=1S/C13H12N4S/c1-2-4-11(5-3-1)6-9-18-13-12-16-15-10-17(12)8-7-14-13/h1-5,7-8,10H,6,9H2"	QGQSZEIXFAHGEY-UHFFFAOYSA-N
MK139-1	C1(OCCC2=CC=CC=C2)=NC=CN3C1=NN=C3C4=CC=CC=C4	"InChI=1S/C19H16N4O/c1-3-7-15(8-4-1)11-14-24-19-18-22-21-17(23(18)13-12-20-19)16-9-5-2-6-10-16/h1-10,12-13H,11,14H2"	BKUOBYRSGGKOSW-UHFFFAOYSA-N
MK091-2	FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC5=C(C=C4)N=CN5)N32)=CC=C1F	"InChI=1S/C20H14F2N6O/c21-14-3-1-12(7-15(14)22)5-6-29-19-10-23-9-18-26-27-20(28(18)19)13-2-4-16-17(8-13)25-11-24-16/h1-4,7-11H,5-6H2,(H,24,25)"	OKICKLNNAMYKHW-UHFFFAOYSA-N
MNB6-8	NC1=C2C(C=C(C3=CC(S(N)(=O)=O)=CC=C3)S2)=NC=N1	"InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)"	MQMXDJVOZKMSNT-UHFFFAOYSA-N

[MFernflower]

@maratsydney Perhaps the RHS benzimidazole?

[MFernflower]

@maratsydney @mattodd @edwintse What if we go for a "RHS primary amine on stilts" approach? E.G www.sigmaaldrich.com/catalog/product/aldrich/741213

[mattodd]

OK, looks good @maratsydney . For the accumulation screen, @edwintse can you advise on any amines we may have? Paul says, re the assay, that for accumulation in E. coli they need the structure (or at least the MW) and a few mgs, in a vial in as dry mass. Also, the compound needs to be soluble up to at least 50 uM in aqueous solution and pure. @mbhebhe can you see if OSM-S-106 is predicted to be any good here? Again aromatic NH2.. @drc007 or @MFernflower do you know if is there a simple way to discover aliphatic amines hiding in the mycetoma Epichem library, out of interest? @bendndi

[edwintse]

@maratsydney @mattodd Yes, that compound now resides in London (but easy to make if needed, the phenylalaninol SM is still at USyd). The only other amine I can think of is the benzylic amine with 2-carbon linker, but I'm fairly certain that we don't have that compound made (maybe Alice did a while ago but not recently). Again that compound fails with high flexibility.

[drc007]

@mattodd I did a couple of substructure queries, there is a single primary aliphatic amine:

EPL-BS0116

237 secondary aliphatic amines are in the library however:

Name,COMPOUND_ID EPL-BS1077,SCYX0001724340 EPL-BS1078,SCYX0001724341 EPL-BS1070,SCYX0001720696 EPL-BS1057,SCYX0001715609 EPL-BS1056,SCYX0001715608 EPL-BS1021,SCYX0001695341 EPL-BS1021,SCYX0001695341 EPL-BS1047,SCYX0001713295 EPL-BS1032,SCYX0001703787 EPL-BS1031,SCYX0001703786 EPL-BS1033,SCYX0001703788 EPL-BS1030,SCYX0001703785 EPL-BS1037,SCYX0001703789 EPL-BS1027,SCYX0001697554 EPL-BS1021,SCYX0001695341 EPL-BS1021,SCYX0001695341 EPL-BS1020,SCYX0001695339 EPL-BS1015,SCYX0001695340 EPL-BS1016,SCYX0001695342 EPL-BS0995,SCYX0001677865 EPL-BS0995,SCYX0001677865 EPL-BS994,SCYX0001677864 EPL-BS0995,SCYX0001677865 EPL-BS0995,SCYX0001677865 EPL-BS0996,SCYX0001677866 EPL-BS1011,SCYX0001684753 EPL-BS1012,SCYX0001684754 EPL-BS0935,SCYX0001614386 EPL-BS0935,SCYX0001614386 EPL-BS0989,SCYX0001676784 EPL-BS0990,SCYX0001676785 EPL-BS0983,SCYX0001676778 EPL-BS0984,SCYX0001676779 EPL-BS0970,SCYX0001639419 EPL-BS0952,SCYX0001625112 EPL-BS0950,SCYX0001625110 EPL-BS0951,SCYX0001625111 EPL-BS0949,SCYX0001625109 EPL-BS0948,SCYX0001625108 EPL-BS0857,SCYX0001599460 EPL-BS0857,SCYX0001599460 EPL-BS0943,SCYX0001625115 EPL-BS0942,SCYX0001625114 EPL-BS0947,SCYX0001625118 EPL-BS0946,SCYX0001625117 EPL-BS0941,SCYX0001625113 EPL-BS0944,SCYX0001625116 EPL-BS0940,SCYX0001614389 EPL-BS0939,SCYX0001614388 EPL-BS0934,SCYX0001614385 EPL-BS0931,SCYX0001614384 EPL-BS0935,SCYX0001614386 EPL-BS0935,SCYX0001614386 EPL-BS0938,SCYX0001614387 EPL-BS0923,SCYX0001610442 EPL-BS0922,SCYX0001610441 EPL-BS0924,SCYX0001610443 EPL-BS0928,SCYX0001613516 EPL-BS0862,SCYX0001602411 EPL-BS0861,SCYX0001599461 EPL-BS0857,SCYX0001599460 EPL-BS0857,SCYX0001599460 EPL-BS0856,SCYX0001599459 EPL-BS0855,SCYX0001599458 EPL-BS0871,SCYX0001602513 EPL-BS0840,SCYX0001596473 EPL-BS0808,SCYX0001576379 EPL-BS0808,SCYX0001576379 EPL-BS0882,SCYX0001607269 EPL-BS0881,SCYX0001607268 EPL-BS0880,SCYX0001607267 EPL-BS0878,SCYX0001607266 EPL-BS0822,SCYX0001578294 EPL-BS0832,SCYX0001596466 EPL-BS0831,SCYX0001596465 EPL-BS0830,SCYX0001596464 EPL-BS0823,SCYX0001578295 EPL-BS0821,SCYX0001578293 EPL-BS0816,SCYX0001576386 EPL-BS0813,SCYX0001576384 EPL-BS0812,SCYX0001576383 EPL-BS0809,SCYX0001576380 EPL-BS0810,SCYX0001576381 EPL-BS0808,SCYX0001576379 EPL-BS0808,SCYX0001576379 EPL-BS0799,SCYX0001574846 EPL-BS0798,SCYX0001574845 EPL-BS0797,SCYX0001574844 EPL-BS0796,SCYX0001574843 EPL-BS0793,SCYX0001574839 EPL-BS0702,SCYX0001499523 EPL-BS0702,SCYX0001499523 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0788,SCYX0001564274 EPL-BS0783,SCYX0001564269 EPL-BS0790,SCYX0001564276 EPL-BS0789,SCYX0001564275 EPL-BS0787,SCYX0001564273 EPL-BS0784,SCYX0001564270 EPL-BS0786,SCYX0001564272 EPL-BS0785,SCYX0001564271 EPL-BS0773,SCYX0001562763 EPL-BS0761,SCYX0001555054 EPL-BS0760,SCYX0001555052 EPL-BS0775,SCYX0001562765 EPL-BS0774,SCYX0001562764 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0746,SCYX0001551241 EPL-BS0722,SCYX0001538109 EPL-BS0726,SCYX0001536085 EPL-BS0723,SCYX0001538110 EPL-BS0721,SCYX0001538108 EPL-BS0720,SCYX0001538107 EPL-BS0719,SCYX0001538106 EPL-BS0711,SCYX0001538102 EPL-BS0712,SCYX0001538103 EPL-BS0710,SCYX0001538101 EPL-BS0702,SCYX0001499523 EPL-BS0702,SCYX0001499523 EPL-BS0668,SCYX0001492867 EPL-BS0669,SCYX0001492868 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0667,SCYX0001492866 EPL-BS0555,SCYX0001460907 EPL-BS0555,SCYX0001460907 EPL-BS0576,SCYX0001465504 EPL-BS0633,SCYX0001489889 EPL-BS0635,SCYX0001489891 EPL-BS0634,SCYX0001489890 EPL-BS0631,SCYX0001489887 EPL-BS0625,SCYX0001468000 EPL-BS0626,SCYX0001468001 EPL-BS0617,SCYX0001467770 EPL-BS0616,SCYX0001467769 EPL-BS0610,SCYX0001465513 EPL-BS0599,SCYX0001465507 EPL-BS0598,SCYX0001465506 EPL-BS0597,SCYX0001465505 EPL-BS0596,SCYX0001465504 EPL-BS0576,SCYX0001464843 EPL-BS0563,SCYX0001462992 EPL-BS0567,SCYX0001462996 EPL-BS0574,SCYX0001454121 EPL-BS0560,SCYX0001462989 EPL-BS0559,SCYX0001462988 EPL-BS0562,SCYX0001462991 EPL-BS0561,SCYX0001462990 EPL-BS0556,SCYX0001460908 EPL-BS0555,SCYX0001460907 EPL-BS0555,SCYX0001460907 EPL-BS0554,SCYX0001460906 EPL-BS0523,SCYX0001454263 EPL-BS0526,SCYX0001454266 EPL-BS0525,SCYX0001454265 EPL-BS0524,SCYX0001454264 EPL-BS0522,SCYX0001454262 EPL-BS0515,SCYX0001454116 EPL-BS0509,SCYX0001454121 EPL-BS0508,SCYX0001454114 EPL-BS0506,SCYX0001449910 EPL-BS0487,SCYX0001449872 EPL-BS0484,SCYX0001449869 EPL-BS0483,SCYX0001449868 EPL-BS0486,SCYX0001449871 EPL-BS0485,SCYX0001449870 EPL-BS0480,SCYX0001449770 EPL-BS0479,SCYX0001449769 EPL-BS0478,SCYX0001449768 EPL-BS0477,SCYX0001449767 EPL-BS0476,SCYX0001449766 EPL-BS0471,SCYX0001449761 EPL-BS0462,SCYX0001449752 EPL-BS0460,SCYX0001449750 EPL-BS0459,SCYX0001449749 EPL-BS0458,SCYX0001449748 EPL-BS0461,SCYX0001449751 EPL-BS0457,SCYX0001449747 EPL-BS0456,SCYX0001449746 EPL-BS0455,SCYX0001449745 EPL-BS0453,SCYX0001449743 EPL-BS0452,SCYX0001435851 EPL-BS0449,SCYX0001435848 EPL-BS0454,SCYX0001449744 EPL-BS0446,SCYX0001435845 EPL-BS0445,SCYX0001435844 EPL-BS0444,SCYX0001435843 EPL-BS0443,SCYX0001435842 EPL-BS0435,SCYX0001435834 EPL-BS0437,SCYX0001435836 EPL-BS0434,SCYX0001435833 EPL-BS0427,SCYX0001435826 EPL-BS0426,SCYX0001435825 EPL-BS0425,SCYX0001435824 EPL-BS0424,SCYX0001435823 EPL-BS0423,SCYX0001435822 EPL-BS0415,SCYX0001435772 EPL-BS0414,SCYX0001435771 EPL-BS0413,SCYX0001435770 EPL-BS0412,SCYX0001435769 EPL-BS0354,SCYX0001434927 EPL-BS352,SCYX0001434925 EPL-BS333,SCYX0001433766 EPL-BS0330,SCYX0001433767 EPL-BS0329,SCYX0001433766 EPL-BS0335,SCYX0001423057 EPL-BS0334,SCYX0001423056 EPL-BS0321,SCYX0001423071 EPL-BS0320,SCYX0001423070 EPL-BS0307,SCYX0001423057 EPL-BS0306,SCYX0001423056 EPL-BS0305,SCYX0001423055 EPL-BS0301,SCYX0001423051 EPL-BS0303,SCYX0001423053 EPL-BS0302,SCYX0001423052 EPL-BS0300,SCYX0001423050 EPL-BS0297,SCYX0001423047 EPL-BS0296,SCYX0001423046 EPL-BS0299,SCYX0001423049 EPL-BS0298,SCYX0001423048 EPL-BS0291,SCYX0001418012 EPL-BS0278,SCYX0001402166 EPL-BS0274,SCYX0001392073 EPL-BS0263,SCYX0001388394 EPL-BS0232,SCYX0001342991 EPL-BS 230,SCYX0001342989 EPL-BS0223,SCYX0001340247 EPL-BS0196,SCYX0001335911 EPL-BS0187,SCYX0001332843 EPL-BS0184,SCYX0001330090 EPL-BS0164,SCYX0001325586 EPL-BS0098,SCYX0001268517 EPL-BS0106,SCYX0001278549

[bendndi]

@drc007 I think this post may have been intended for a MycetOS thread?

[mattodd]

Hi @bendndi - if it looks like we might want to take some of these Epichem compounds and put them in a screen of the kind described above, then yes we can move it over there. Looks like there might be relevant compounds, so the next stage would be to i) see how they do in the online search tool and b) see if we actually want to evaluate them. If this looks at all promising, let's move that discussion over to there, sure. This post usefully has all the context.

[bendndi]

@mattodd -my bad I hadn't read the entire thread and when I saw the epichem library I assumed it was intended fora Mycetos thread....

[MFernflower]

@mattodd @bendndi I ran the first 5 of the set of sec amines @drc007 posted and they all failed on the flexibility front - also it seems the software specifically asks for a primary amine but can recognize secondary amines as failing?

However it might be worth sending out primary amine EPL-BS0116 if we can ship it before deadline!!!!!!

In brief I do not think the s1 osmy compounds will show antibiotic activity but I could potentially be pleasantly surprised

[maratsydney]

The post above was updated: as per @MFernflower 's request the benzimidazole compound (MK091-2) was added along with MNB6-8 (OSM-106) from @mbhebhe.

Compounds were shipped today and should make it to Brisbane on Monday.

[MFernflower]

@mattodd @maratsydney @edwintse Methinks we should spin off the compounds physically sent to Brisbane into a new issue so we can discuss results when they come in!

[MFernflower]

@MatTodd is the coadd screen only going to be against bacterial organisms or will fungi be included?

[mattodd]

Details are on the COADD website. From memory, two fungi.

On Tue, 4 Dec 2018 at 18:04, MFernflower notifications@github.com<mailto:notifications@github.com> wrote:

@mattoddhttps://github.com/mattodd is the coadd screen only going to be against bacterial organisms or will fungi be included?

— You are receiving this because you were mentioned. Reply to this email directly, view it on GitHubhttps://github.com/OpenSourceMalaria/OSM_To_Do_List/issues/577#issuecomment-444198005, or mute the threadhttps://github.com/notifications/unsubscribe-auth/AELtNTmPMhZ7kayWGIcQua55rzvnWZ3dks5u1rk2gaJpZM4YvfmH.

-- Professor Matthew H. Todd Chair of Drug Discovery University College London

UCL School of Pharmacy 29-39 Brunswick Square London WC1N 1AX

T +44 207 753 5568; M +44 7842 483526 E matthew.todd@ucl.ac.ukmailto:matthew.todd@ucl.ac.uk; Tw @mattoddchem W ucl.ac.uk/pharmacy/http://ucl.ac.uk/pharmacy/; opensourcemalaria.org/http://opensourcemalaria.org/; opensourcepharma.net/http://opensourcepharma.net/

[MFernflower]

@mattodd coadd mentions a "confidentially period that can be extended at request - can we request coadd to allow us to push the data to github as soon as they have it

[mattodd]

Let confidentiality period = zero

[MFernflower]

Closing this issue per https://github.com/OpenSourceMalaria/Series4/issues/64 @mattodd