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Егоров Н.С., Баранова Н.А., Крейер В.Г. Московский государственный университет им. М.В. Ломоносова
АНТИБИОТИКИ И ХИМИОТЕРАПИЯ, 1999-N5, стр. 38-44. В начало...
(Окончание)
В последние годы японскими учеными ведутся интенсивные исследования по поиску микробных ингибиторов ацил-КоА-холестерин-ацилтрансферазы (КФ 2.3.1.26) (АХАТ). Это связано с возможным практическим применением этих соединений.
Известно, что в плазме крови содержатся эфиры холестерина и жирных кислот и свободный холестерин, причем количество эфиров холестерина в два раза выше количества свободного холестерина. Не исключено, что на основе ингибиторов АХАТ возможно создание серии новых медицинских препаратов для борьбы с атеросклерозом.
Ингибиторы АХАТ образуются различными видами микроорганизмов, в том числе мицелиальными грибами, относящимися к родам Peniсillium, Aspergillus, Stachybotrys, Gliocladium и др., и имеют различную химическую структуру. Некоторые данные о микробных ингибиторах АХАТ приведены в табл. 2.
| Таблица 2. Микробные ингибиторы ацетил-КоА-холестерин-ацилтрансферазы (АХАТ) |
| Продуцент |
Ингибитор |
Ингибиторная активность, ИK50 |
Литературная ссылка |
| Pseudomonas sр. А92 |
Акатерин |
120 мкМ (АХАТ из микросом печени крыс); 45 мкМ
(АХАТ из макрофагов J774) |
[44] |
Peniсillium asperosporum
KY 1635 |
AS-186 |
Для AS-186 a, b, c, d и g - 22,9; 8,2; 11,3; 12,4 и 13,9 мкМ соответственно (АХАТ из микросом печени кролика) |
[45] |
| Stachybotrys bibyi |
Эпи-кохлохинон A |
1,7 мкМ (АХАТ из микросом печени крыс) |
[46] |
| Aspergilius fumigatus F-37 |
GERI-BP 001 |
Для GERI-BP 001 M, A и B - 42; 94 и 40 мкМ соответственно (АХАТ из микросом печени крыс) |
[47] |
| Aspergillus fumigatus F-93 |
GERI-BP 002A |
50 мкМ (АХАТ из микросом печени крыс) |
[48] |
| Gliocladium sр. FO 1513 |
Глизопренины |
Для глизопренинов А и В - 46 и 61 мкМ соответственно (АХАТ из микросом печени крыс) и 1,2 и 0,57 мкМ соответственно (АХАТ из макрофагов J774) |
[49] |
| Bacillus sp. A 1238 |
Изогалобациллин |
50 мкМ (АХАТ из макрофагов J774) |
[50] |
Peniсillium multicolor
FO-3216 |
Изохромофилоны |
Для изохромофилонов III, IV, V и VI - 110; 50; 50 и 120 мкМ соответственно (АХАТ из микросом печени крыс) |
[51] |
| Gibberella lateritium IFО 7188 |
Латеритин |
5,7 мкМ (АХАТ из микросом печени крыс) |
[52] |
Aspergillus fumigatus
FO 1289-2501 |
Пирипиропены |
Для пирипиропена М - 3,8 мкМ; для пирипиропенов от N до R - 11,0-78,0 мкМ (АХАТ из микросом печени крыс) |
[53-55] |
Albophoma yamanashiensis
FO-2346 |
Терпендолы |
Для терпендолов А, В, Си D - 15,1; 26,8; 2,1 и 3,2 мкМ соответственно (АХАТ из макрофагов J774) |
[56, 57] |
| Peniсillium purpurogenum FO-608 |
Пурпактины |
Для пурпактинов А, В и С - 121-126 мкМ (АХАТ из микросом печени крыс) |
[58, 59] |
АНТИБИОТИКИ И ХИМИОТЕРАПИЯ, 1999-N5, стр. 38-44.
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45. Kuroda K., Morishita Y., Saito Y. et al. AS-186 compounds, new inhibitors of acyl-CoA-cholesterol acyltransferase from Penicillium asperosporum KY 1635. Ibid 47: 1: 16-23.
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47. Jeong T.S., Kim S.U., Son K.H. et al. GERI-BP 001 compounds, new inhibitors of acyl-CoA-cholesterol acyltransferase from Aspergillus fumigatus F-37. I. Production, isolation and physico-chemical and biological properties. Ibid 1995; 48: 8: 751-757.
48. Kim J.K., Lее H.W., Son K.H. et al. GERI-BP 002-A, novel inhibitor of acyl-CoA-cholesterol acyltransferase produced by Aspergillus fumigatus F-93. Ibid 1996; 49: 1: 31-37.
49. Tomoda H., Huang X.H., Nishida H. et al. Glisoprenins, new inhibitors of acуl-CoA-colesterol acyltransferase producd by Gliocladium sр. FO-1513. I. Рrоduction, isolation and physico-chemical and biological properties. Ibid; 1992; 45: 8: 1202-1206.
50. Hasumi К., Takizawa К., Takahashi F. et al. Inhibition of acуl-coenzyme-cholesterol acyltransferase by isohalobacillin, a complex of novel cyclic acylpeptides produced by Bacillus sр. A 1238. Ibid; 1995; 48: 12: 1419-1425.
51. Arai N., Shiomi K., Tomoda H. et al. Isochromophilones III-VI inhibitors of acyl-CoA-cholesterol acyltransferase produced by Penicillium multicolor. Ibid 1995; 48: 7: 696-702.
52. Hasumi К., Shinohara Ch., lwanaga Т., Endo A. Lateritin, a new inhibitor of acyl-CoA-cholesterol acyltraneferase poduced by Gibberella lateritium IFO 7188. Ibid 1993; 46: 12: 1782-1787.
53. Tomoda H., Kim Y.K., Nishida H. et al. Pyripyropenes, novel inhibitors of acyl-CoA-cholesterol acyltransferase produced by Aspergillus fumigatus: 1. Production, isolation and biological properties. Ibid 1994; 47: 2: 148-154.
54. Tomoda H., Tabata N., Yang D.J. et al. Pyripyropenes, novel acyl-CoA-cholesterol acyltransferase inhibitors produced by Aspergillus fumigatus. 3. Structure elucidation of pyripyropenes E to L. Ibid 1995; 48: 6: 495-504.
55. Tomoda H., Tabata N., Yang D.J. et al. Pyripyropenes, novel inhibitors of acyl-CoA-cholesterol аcу1transferase produced by Aspergillus fumigatis: 4. Structure elucidation of pyripyropenes M to R. Ibid; 1996; 49: 3: 292-299.
56. Huang X.H., Nishida H., Tomoda H. et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. II. Structure elucidation of terpendoles A, B, C and D. Ibid 1995; 48: 1: 5-11. 57. Huang X.H., Tomoda H., Nishida H. et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties. Ibid 1-4.
58. Hirota H., Hashimoto M., Kohasaka M. Purpactins, new inhibitors of acyl-CoA-cholesterol acyltransferase produced by Penicillium purpurogenum. I. Production, isolation and physico-chemical and biological properties. Ibid 1991; 44: 2: 136-143.
59. Hishida H., Tomoda H., Ying Cao et al. Purpactins, new inhibitors acyl-CoA-cholesterol acyltransferase produced by Penicillium purpurogenum. II. Structure elucidation of purpactins A, B and C. Ibid 144-151.
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