The panorama of cyclosporin research

Abstract

Cyclosporin, a novel drug, exhibiting unique discriminatory action on the activation of helper lymphocytes without the undesirable side effects associated with conventional immunosuppressants, can well be considered as the prototype of a new generation of immunosuppressants. It is probably the first one to demonstrate that an immunopharmacologic approach to the modulation of the immune response by drugs is feasible. This enabled a decisive step forward to be made in transplantation surgery, particularly in the field of heart and kindney transplantation.Cyclosporin A exerts antifungal, antiparasitic and antiinflammatory activities also. There is considerable interest in the prospective value of this drug in the treatment of autoimmune disorders. Accolades are to be given for its role as a tool for studying mechanisms of the immune system. This review is an attempt to look into the various strides it had evolved before attaining the status of a unique drug, and also to assess critically the prospective value of this potent drug.The present modem era of antibiotic research is characterized by advanced screening procedures aiming specifically not only at antibacterials or antifungals but at compounds like enzyme inhibitors, immunomodulators and antitumor drugs. New sources of rare microorganisms are currently under exploitation. Development of microbial products with new medicinal activties has turned out to be a big research area, spearheaded by the success story of small molecular weight immunomodulators. Long accepted as the best way to prevent or treat rejection in patients undergoing organ transplantation, immunosuppressive therapy is attracting increased attention for its ability to treat a variety of diseases. One such potent agent, widely acclaimed as the first of a new generation of remarkable immunosuppressive agents, cyclospofin is being used in novel ways in a wide array of conditions.The cyclosporins are a group of over 25 closely related cyclic undecapeptides produced as secondary metabolites by two strains of fungi imperfecti, Cylindrocarpum lucidum BOOTH and Tolypocladium inflaturn CAMS, isolated from soil samples. Cyclosporin A is the main component of this family of cyclic peptides each containing 11 amino acids.This review is a survey of the works of a large team of chemists, biologists, clinicians, toxicologists and pharmacologists which lead to the development of a new drug of choice and the impact that this drug in particular is having and hopefully other similar ones will have in the field of immunopharmacology. Discovery of cyclosporinThe cyclosporins were originally discovered in 1970 by scientists at Sandoz Laboratory in Switzerland while attempting to identify new antifungal agents [ 11. Crude extracts of two new 9 J. Basic Microbiol. 36 (1996) 2 122 K. BALAKRISHNAN AND A. PANDEY strains of fungi imperfecti Cylindrocarpon lucidium, BOOTH and Tolypocladium inflaturn CAMS demonstrated a narrow spectrum of activity in vitro mainly against clinically irrelevant organisms. However, the antifunga...

Solution conformations of cyclosporins and magnesium‐cyclosporin complexes determined by vibrational circular dichroism

“…Of the 11 amino acids, MeBmt-1 appears to be the most important, in relation to biological activity, although it is a combination of residues 1, 2, 3, 9, 10, and 11 that affects the bioactivity of cyclosporins. 22 Cyclosporin C, containing a hydroxyl group from the threonine residue at position 2, also exhibits strong immunosuppressive activity, 22 and adopts a similar solution 21 and crystal 24 conformation to CsA. Substituting a more branched alkyl residue at position 2 (CsD) leads to a slight decrease in immunosuppressive activity, 22 even though CsD adopts a similar backbone conformation to CsA in solution.…”

“…22 In addition to CsA, cyclosporins C, D, G, and H have been examined by IR 21 and/or X-ray crystallographic 23 techniques, and the corresponding metal complexes have been studied using IR spectroscopy. Of the 11 amino acids, MeBmt-1 appears to be the most important, in relation to biological activity, although it is a combination of residues 1, 2, 3, 9, 10, and 11 that affects the bioactivity of cyclosporins.…”

Remediation of Textile Dye Waste Water Using a White-Rot Fungus Bjerkandera adusta Through Solid-state Fermentation (SSF)

“…Many of the solid materials used as the main substrates for SSF are unrefined and are of agricultural origin [6,7]. Their complex and unrefined composition makes the complete characterisation and exact reproducibility of such fermentation processes very difficult [8].…”

Differentiation of cyclosporin A from isocyclosporin A by liquid chromatography/electrospray ionization mass spectrometry with post-column addition of divalent metal salt

“…). It is a well‐known commercial cyclic undecapeptide with immunosuppressing activity, and is used in bone marrow and organ transplantation treatment . This compound has also a variety of other biological properties, which include anti‐inflammatory, antifungal and antiparasitic activities .…”