Lincomycin analogs show antimalarial activity - C&EN Global

Nov 6, 2010 - NIH is planning tests against additional strains of simian malaria before making a decision on whether to conduct clinical tests. Althou...
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AC3 meeting Action oriented

AC 3 has encouraged the develop­ ment of teaching aids such as films and film loops, and has promoted work­ shops in computer-assisted instruction. Recent resource papers include "Bio­ chemistry in the Introductory Chem­ istry Course" and "Combustion and Flame." Since its meeting last March in New Orleans, the council has sponsored top­ ical conferences on biochemistry in the chemistry curriculum, unified lab­ oratories, conceptual structures for in­ terdisciplinary courses, and the chem­ istry teacher and two-year colleges. Regional conferences on curriculum problems have been held in Louisville, Ky.; Lewisburg, Pa.; Worcester, Mass.; Charlotte, N.C.; Moscow, Idaho; and Pullman, Wash. A recent activity of AC 3 is its con­ sultant service, established this fall. AC 3 will provide consultants to work closely with institutions that want help to improve their undergraduate courses in chemistry and in planning future de­ partment development. Course and curriculum content, staff needs, and visual aids are among the subjects within the purview of the consultants.

Eimac unit generates UV light having "clean" spectral band Higher resolution ultraviolet spec­ troscopy and precise measurements of UV-induced photochemical reac­ tions should be possible because of a new ultraviolet light source developed by Eimac in San Carlos, Calif., a divi­ sion of Varian Associates. The novel, electrodeless lamp generates light that has a very "clean" spectral band and high power readings. The lamp can be used in extrater­ restrial solar simulation irradiation work. For such work, the light should be in the 4000- to 1000-A. region and have higher power density than has been available until now. The power density of UV light emitted by the new lamp is three to 10 times higher 24 C&EN NOV. 13r 1967

than that of UV light from previous sources. Because of this higher power density, it's possible to detect more precisely the components in a gas mix­ ture, an important aid in studying the composition of upper-atmosphere gas. Eimac doesn't have precise values for the power density, however. UV light is generated when a mix­ ture of gases, enclosed in a tube, is exposed to 2450-MHz. microwave en­ ergy, Dr. Leonard Reed, Eimac's ad­ vanced products manager, says. The current experimental unit, which is four inches long and has a wall thick­ ness of V 8 inch, is made of alumina. A sapphire lens at one end transmits light down to a wave length of 1600 A. Substitution of lanthanum fluoride or lithium fluoride for the sapphire al­ lows passage of light in the 1600- to 1200-A. range. It's also possible to tailor the UV light wave length to narrow limits by filling the tube with a preselected mixture of gases. Light in the spec­ tral region of 1900 A. to 1700 Α., for example, results from using a mixture of 20 parts nitrogen and 80 parts argon. Other gases, such as xenon, krypton, helium, and hydrogen, pro­ duce UV light of specific wave length. One of the lamp's features is that the power of the emitted light can be varied by adjusting the microwave power input, according to Dr. Reed and project engineer Jared Leidigh who jointly developed the device. They have pushed input power as high as 900 watts. By comparison, con­ ventional UV lamps have a maximum input rating of 100 watts. It should be possible to go higher in power, they believe, by switching from alu­ mina to a water-cooled beryllia tube that can withstand microwave input power greater than 900 watts. Construction of the lamp involves some interesting technology. The crystal sapphire window at one end and the gas input tubulation and valve at the other are sealed to the alumina by means of special metallurgical brazing methods developed at Eimac. The entire unit is baked at 500° C. while the lamp chamber is maintained at high vacuum to ensure that all im­ purities are removed from the walls of the chamber. Then, the tube is filled with pure gas or a gas mixture until it reaches a pressure of 1.5 torr at room temperature. The lamp is inserted into a micro­ wave resonance cavity linked to a 2.5-kw. microwave generator. Dr. Reed estimates that it should be good for several hundred hours of continu­ ous operation before it needs degass­ ing and refilling. A conventional UV lamp, by comparison, has an average in-service life of only 10 hours, he notes.

Lincomycin analogs show antimalarial activity Analogs of lincomycin, a widely used medium-spectrum antibiotic, may be useful in the treatment of malaria, ac­ cording to microbiologists at The Up­ john Co. Charles Lewis of the com­ pany's Kalamazoo, Mich., research laboratory says that one of the new compounds, 7-chloro-N-demethyl4'-pentyl-lincomycin, is as effective as chloroquine against Plasmodium berghei, a malarial strain that affects mice. Tests at the National Institutes of Health have confirmed the Upjohn tests in mice, and limited studies with monkeys show the compound is effec­ tive against Plasmodium cynomologi. NIH is planning tests against addi­ tional strains of simian malaria before making a decision on whether to con­ duct clinical tests. Although P. berghei does not infect humans, strains of this malaria-produc­ ing organism which resist chloroquine and diaminodiphenyl sulfone ( D D S ) , the most commonly used antimalarial drugs, were knocked out by the new compounds. This leads Mr. Lewis to speculate that the same will hold for human forms of the disease. Furthermore, the lincomycin ana­ logs are not related to or cross-resistant with chloroquine and DDS, leading to the supposition that they inhibit growth of the parasite by a different method. One possibility suggested by Mr. Lewis is the suppression of vital biochemical processes, such as protein synthesis, at the ribosomal level in the infecting organisms. Testing antibiotics against malaria is not new. Most broad-spectrum an­ tibiotics are routinely screened for an­ timalarial activity. Some, including such common ones as oxytetracycline, chloroamphenicol, and chlorotetracycline, show some but not useful activ­ ity. In general, these antibiotics act relatively slowly against malaria-pro­ ducing organisms. In addition to 7-chloro-N-demethyl4'-pentyl-lincomycin, Mr. Lewis and his coworkers have tested other deriv­ atives of lineomycin for antimalarial activity. The most active against P. berghei were chlorinated at C-7. The parent compound and nonhalogenated analogs showed no activity. The increased antimalarial activity caused by chlorine substitution at C-7 parallels the increase in general anti­ microbial activity of lincomycin de­ rivatives. Upjohn workers had pre­ viously found that the 7-halogenated derivatives, which were synthesized by Dr. B. J. Wagerlein, Dr. F. Kagan, and R. D. Birkenmeyer, showed an antibiotic activity four times as great as the parent compound.