ID: ALA399043

Max Phase: Preclinical

Molecular Formula: C11H14O2S

Molecular Weight: 210.30

Molecule Type: Small molecule

Representations

Synonyms (4): (5R)-Thiolactomycin | (R)-(+)-Thiolactomycin | 5R-Thiolactomycin | Thiolactomycin
Synonyms from Alternative Forms(4):

Canonical SMILES:  C=C/C(C)=C/[C@@]1(C)SC(=O)C(C)=C1O

Standard InChI:  InChI=1S/C11H14O2S/c1-5-7(2)6-11(4)9(12)8(3)10(13)14-11/h5-6,12H,1H2,2-4H3/b7-6+/t11-/m1/s1

Standard InChI Key:  SYQNUQSGEWNWKV-XUIVZRPNSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 210.30

Molecular Weight (Monoisotopic): 210.0715

AlogP: 2.98

#Rotatable Bonds: 2

Polar Surface Area: 37.30

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 2

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 6.82

CX Basic pKa:

CX LogP: 2.55

CX LogD: 1.87

Aromatic Rings: 0

Heavy Atoms: 14

QED Weighted: 0.71

Np Likeness Score: 2.23

References

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2. Senior SJ, Illarionov PA, Gurcha SS, Campbell IB, Schaeffer ML, Minnikin DE, Besra GS..  (2004)  Acetylene-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme.,  14  (2): [PMID:14698162] [10.1016/j.bmcl.2003.10.061]

3. McFadden JM, Medghalchi SM, Thupari JN, Pinn ML, Vadlamudi A, Miller KI, Kuhajda FP, Townsend CA..  (2005)  Application of a flexible synthesis of (5R)-thiolactomycin to develop new inhibitors of type I fatty acid synthase.,  48  (4): [PMID:15715465] [10.1021/jm049389h]

4. McFadden JM, Medghalchi SM, Thupari JN, Pinn ML, Vadlamudi A, Miller KI, Kuhajda FP, Townsend CA..  (2005)  Application of a flexible synthesis of (5R)-thiolactomycin to develop new inhibitors of type I fatty acid synthase.,  48  (4): [PMID:15715465] [10.1021/jm049389h]

5. Kim P, Zhang YM, Shenoy G, Nguyen QA, Boshoff HI, Manjunatha UH, Goodwin MB, Lonsdale J, Price AC, Miller DJ, Duncan K, White SW, Rock CO, Barry CE, Dowd CS..  (2006)  Structure-activity relationships at the 5-position of thiolactomycin: an intact (5R)-isoprene unit is required for activity against the condensing enzymes from Mycobacterium tuberculosis and Escherichia coli.,  49  (1): [PMID:16392800] [10.1021/jm050825p]

6. Ohata K, Terashima S..  (2007)  Synthesis and biological activity of enantiomeric pairs of 5-vinylthiolactomycin congeners.,  17  (14): [PMID:17507223] [10.1016/j.bmcl.2007.04.067]

7. Bhowruth V, Brown AK, Senior SJ, Snaith JS, Besra GS..  (2007)  Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library.,  17  (20): [PMID:17766110] [10.1016/j.bmcl.2007.07.082]

8. Lee PJ, Bhonsle JB, Gaona HW, Huddler DP, Heady TN, Kreishman-Deitrick M, Bhattacharjee A, McCalmont WF, Gerena L, Lopez-Sanchez M, Roncal NE, Hudson TH, Johnson JD, Prigge ST, Waters NC..  (2009)  Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.,  52  (4): [PMID:19191586] [10.1021/jm8008103]

9. Ondeyka JG, Zink DL, Young K, Painter R, Kodali S, Galgoci A, Collado J, Tormo JR, Basilio A, Vicente F, Wang J, Singh SB..  (2006)  Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as antimicrobial agents using a new antisense-based strategy.,  69  (3): [PMID:16562839] [10.1021/np050416w]

10. Ohata K, Terashima S..  (2008)  Synthesis and biological activity of enantiomeric pairs of 5-[(E)-cycloalk-2-enylidenemethyl]thiolactomycin congeners.,  18  (20): [PMID:18805004] [10.1016/j.bmcl.2008.08.103]

11. Lee JY, Jeong KW, Lee JU, Kang DI, Kim Y..  (2009)  Novel E. coli beta-ketoacyl-acyl carrier protein synthase III inhibitors as targeted antibiotics.,  17  (4): [PMID:19185501] [10.1016/j.bmc.2009.01.004]

12. Lee JY, Jeong KW, Shin S, Lee JU, Kim Y..  (2009)  Antimicrobial natural products as beta-ketoacyl-acyl carrier protein synthase III inhibitors.,  17  (15): [PMID:19595597] [10.1016/j.bmc.2009.06.059]

13. Hans RH, Gut J, Rosenthal PJ, Chibale K..  (2010)  Comparison of the antiplasmodial and falcipain-2 inhibitory activity of beta-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids.,  20  (7): [PMID:20206517] [10.1016/j.bmcl.2010.02.017]

14. Prado-Prado FJ, García-Mera X, González-Díaz H..  (2010)  Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.,  18  (6): [PMID:20185316] [10.1016/j.bmc.2010.01.068]

15. Diamandis P, Wildenhain J, Clarke ID, Sacher AG, Graham J, Bellows DS, Ling EK, Ward RJ, Jamieson LG, Tyers M, Dirks PB..  (2007)  Chemical genetics reveals a complex functional ground state of neural stem cells.,  3  (5): [PMID:17417631] [10.1038/nchembio873]

16. PubChem BioAssay data set, 

17. Hans RH, Wiid IJ, van Helden PD, Wan B, Franzblau SG, Gut J, Rosenthal PJ, Chibale K..  (2011)  Novel thiolactone-isatin hybrids as potential antimalarial and antitubercular agents.,  21  (7): [PMID:21376591] [10.1016/j.bmcl.2011.02.008]

18. PubChem BioAssay data set, 

19. Lee JY, Jeong KW, Shin S, Lee JU, Kim Y..  (2012)  Discovery of novel selective inhibitors of Staphylococcus aureus β-ketoacyl acyl carrier protein synthase III.,  47  [PMID:22104972] [10.1016/j.ejmech.2011.10.052]

20. Abramson HN..  (2011)  The lipogenesis pathway as a cancer target.,  54  (16): [PMID:21726077] [10.1021/jm2005805]

21. Balaji NV, Hari Babu B, Subbaraju GV, Purna Nagasree K, Murali Krishna Kumar M..  (2017)  Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents.,  27  (1): [PMID:27894872] [10.1016/j.bmcl.2016.11.047]

22. Laev SS, Salakhutdinov NF, Lavrik OI..  (2017)  Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1).,  25  (9): [PMID:28161249] [10.1016/j.bmc.2017.01.028]

23. Bommineni GR, Kapilashrami K, Cummings JE, Lu Y, Knudson SE, Gu C, Walker SG, Slayden RA, Tonge PJ..  (2016)  Thiolactomycin-Based Inhibitors of Bacterial β-Ketoacyl-ACP Synthases with in Vivo Activity.,  59  (11): [PMID:27187871] [10.1021/acs.jmedchem.6b00236]

24. Bera S, Mondal D..  (2019)  Insights of synthetic analogues of anti-leprosy agents.,  27  (13): [PMID:31103404] [10.1016/j.bmc.2019.04.032]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays