Not quoting anybody here, -- Antidotally, propolacticly, intervectmin, -- just a few of the misspelled words seen in posts in the last week or so. Don't you guys use a spell checker? Speaking of ivermectin (quoted material follows) --
The avermectins are a group of related, 16-member, naturally occurring or semisynthetic macrocyclic lactone endectocides. They are produced from the fermentation products of the soil-dwelling actinomycete, Streptomyces avermitilis. The avermectins effectively control gastrointestinal nematodes, ticks, mites, lice, cattle grubs, and lungworms. Ivermectin, the most widely used and studied of the avermectins, has a wide therapeutic index, and is an effective treatment for scabies in humans.
The anthelmintic program at the Merck Sharp Dohme Research Laboratories (MSDRL) began in 1953. Building on the experience gained from human health directed antibiotics, Merck Research subsequently decided to explore fermentation broths as a source of new anthelmintics. Wisely, the animal health team chose to use an in vitro screen in mice as the primary assay for fermentation products.
The use of microorganisms including both bacteria and fungi to achieve chemical transformation was not new and was employed also at Squibb, Upjohn, Merck, and by Wettstein and coauthors. Today it seems amusing that some synthetic organic chemists initially took a dim view of the use of microorganisms in a synthetic endeavor, which they regarded as ‘cheating.’ The introduction of the 1,2 double bond via the use of microorganisms became routine thereafter.
Organic chemistry is the foundation of medicinal chemistry. I was very fortunate that Professor William S. Johnson of the University of Wisconsin, Madison, accepted me as a graduate student in 1946. My PhD thesis involved natural product total synthesis, and the target was a steroid. My knowledge of natural product total synthesis made me an attractive candidate for the pharmaceutical industry, for reasons that have remained a tradition widely accepted by big Pharma, but not by biotech companies. The attraction of a natural product as a synthetic target lies in part in the fact that the target was set by Nature, which gives it an aura of legitimacy.
I remember discussing that issue with the late Dr Michael H. Fisher, an outstanding, softly spoken scientist who was responsible for the chemistry of animal health research at Merck. Given that avermectin has five double bonds, I was not very optimistic that we would be able to increase safety in a cost-effective way. Dr Fisher's more optimistic outlook was fully vindicated by subsequent developments. The medicinal chemists succeeded in selectively reducing the C 22–23 double bond in good yield. The resulting dihydroavermectin (ivermectin) was actually slightly less potent than avermectin B1, but, to our delight, it displayed a therapeutic index superior to that of its natural product precursor.
It was also exciting to discover that avermectin and ivermectin are not only broad-spectrum anthelmintics, but also insecticides and acaricides. As Dr Campbell pointed out the activity ‘‘against arthropods changed the scientific and commercial prospects dramatically. When ivermectin was eventually launched as a product for cattle, it was offered not as an anthelmintic, but as an antiparasitic agent for the control of endoparasites and ectoparasites.’’
Sadly, public opinion of the industry is presently at a low point. To a certain degree the industry itself has become a political football, a matter of concern cited by Mr Merck already in 1950. We suspect, however, that even the industry’s most severe critics would not wish their families to be deprived of the medications discovered by the industry during the past 15 years.
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Note: Scabies is caused by an ectoparasitic mite. Ivermectin should not be used to treat or prevent COVID-19. Posted by PLB
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