Antibacterial compounds
View Patent ↗This invention relates to a novel purified compound PM181104, of formula: of molecular weight 1514 and molecular formula C 69 H 66 N 18 O 13 S 5 ; which is obtained by fermentation of the microorganism belonging to Kocuria species (ZMA B-1/MTCC 5269). The invention includes all stereoisomeric forms and all tautomeric forms of the compound PM181104 and pharmaceutically acceptable salts and derivatives such as esters and ethers. The present invention further relates to processes for the production of the novel antibacterial compound(s), to the production of the microorganism belonging to Kocuria species (ZMA B-1/MTCC 5269), and to pharmaceutical compositions containing the novel compound(s) as an active ingredient and its/their use in medicines for treatment and prevention of diseases caused by bacterial infections.
1. A compound of formula I:
wherein R is H, alkyl, alkylcarbonyl, (HO) 2 PO—, alkyl-OPO(OH)—, (alkyl-O) 2 PO—, cycloalkyl, cycloalkylcarbonyl, aryl, arylcarbonyl, heterocyclyl or heterocyclyl carbonyl; or a pharmaceutically acceptable salt thereof, wherein if R is H then the compound is isolated.
2. The compound as claimed in claim 1 , wherein R is H, named PM 181104, or a pharmaceutically acceptable salt thereof.
3. The compound PM181104 as claimed in claim 2 , wherein the compound PM 181104 has antibacterial activity, is isolated from the fermented broth of the microorganism belonging to Kocuria species (ZMA B-1/MTCC 5269) and is characterised by:
(a) the molecular weight of 1514,
(b) the molecular formula C 69 H 66 N 18 O 13 S 5 ,
(c) the UV spectrum as depicted in FIG. 1 ,
(d) the IR spectrum as depicted in FIG. 2 ,
(e) the 1 H NMR spectrum as depicted in FIG. 3 , and
(f) the 13 C NMR spectrum as depicted in FIG. 4 .
4. A process for the production of the compound PM 181104 as claimed in claim 2 , comprising the steps of:
(a) cultivating the microorganism Kocuria species (ZMA B-1/MTCC 5269) under submerged aerobic conditions in a nutrient medium containing sources of carbon and nitrogen to produce the compound PM 181104,
(b) isolating the compound PM 181104 from the fermented broth, and
(c) purifying the compound PM 181104.
5. A process as claimed in claim 4 , further comprising the step of converting the compound PM 181104 to its pharmaceutically acceptable salt.
6. A process as claimed in claim 4 , further comprising the step of reacting the compound PM181104 with an acid having the formula RCOOH; wherein R is alkyl, cycloalkyl, aryl or heterocyclyl, to obtain the novel compounds of formula I
wherein is alkyl, cycloalkyl, aryl or heterocyclyl.
7. The compound as claimed in claim 1 wherein R is
8. A pharmaceutical composition, comprising an effective amount of the compound as claimed in claim 1 , with at least one pharmaceutically acceptable excipient or an additive or an auxiliary.
9. The pharmaceutical composition as claimed in claim 8 , wherein the pharmaceutical composition is in the form of a tablet, coated tablet, capsule, granule, powder, cream, ointment, gel, emulsion, suspension, or solution for injection.
10. A pharmaceutical composition as claimed in claim 8 , wherein said composition is adapted for the treatment of gram-positive bacterial infection.
11. The pharmaceutical composition as claimed in claim 10 , wherein said bacterial infection is caused by bacteria belonging to Staphylococcus, Streptococcus, Enterococcus or Bacillus species.
12. The pharmaceutical composition as claimed in claim 11 , wherein said bacteria belong to Staphylococcus or Enterococci species.
13. The pharmaceutical composition as claimed in claim 12 , wherein said bacteria belonging to Staphylococcus species is methicillin-resistant.
14. The pharmaceutical composition as claimed in claim 12 , wherein said bacteria belonging to Staphylococcus species is vancomycin-resistant.
15. The pharmaceutical composition as claimed in claim 12 , wherein said bacteria belonging to Enterococci species is vancomycin-resistant.
16. A method of treating a bacterial infection comprising administering to a mammal in need thereof an effective amount of a compound as claimed in claim 1 , wherein the bacterial infection is caused by a gram-positive bacteria.
17. The method as claimed in claim 16 , wherein the bacterial infection is caused by bacteria belonging to Staphylococcus, Streptococcus, Enterococci and Bacillus species.
18. The method as claimed in claim 17 , wherein the bacterial infection is caused by bacteria belonging to Staphylococcus or Enterococci species.
19. The method as claimed in claim 18 , wherein said bacteria belonging to Staphylococcus species is methicillin-resistant.
20. The method as claimed in claim 18 , wherein said bacteria belonging to Staphylococcus species is vancomycin-resistant.
21. The method as claimed in claim 18 , wherein bacteria belonging to Enterococci species is vancomycin-resistant.