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Streptomyces Host-Vector Systems
Published in Yoshikatsu Murooka, Tadayuki Imanaka, Recombinant Microbes for Industrial and Agricultural Applications, 2020
Anthracyclines consist of an anthracyclinone (aglycone) to which one or more sugars are attached. The anthracyclinone is believed to be produced by the polyketide synthetase system. Daunorubicin (daunomycin) and doxorubicin (Adriamycin), which belong to the anthracycline antibiotics, are commercially important antibiotics with potent antitumor activity. In 1990 [23], genes for the biosynthesis of daunorubicin and doxorubicin were cloned from S. peucetius and S. peucetius subsp. caesius, respectively, by using DNA fragments carrying polyketide synthetase genes from S. coelicolor [20] and S. glaucescens [24] as probes. Here, cosmid libraries were screened by colony hybridization for clones that hybridized to S. coelicolor actl and actlll [20], and S. glaucescens tcmla genes [24]. The restriction mapping revealed that the DNA represented three nonoverlapping regions of the S.peucetius subsp. caesius genome. Tetracenomycin C, produced by S. glaucescens, is also an anthracycline antibiotic. Montamedi and Hutchinson [24] have cloned all of the genes for the production of tetracenomycin C into pIJ702, through complementation of mutations specifically blocking the biosynthesis of tetracenomycin C by S. glaucescens and selecting for resistance to the drug in S. lividans. The tetracenomycin C biosynthetic and resistance genes form a single cluster in the S. glaucesens genome and are expressed in heterologous streptomycete hosts such as S. lividans.
Applications of Liposomal Drug Delivery Systems to Cancer Therapy
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
The drugs most frequently incorporated and evaluated in liposomal formulations are anthracyclines, including doxorubicin and daunorubicin. The choice of doxorubicin by many of the early research groups examining the role of liposomes as drug carriers in cancer chemotherapy stems from its broad spectrum of anti-tumor activity on the one hand, and its disturbing cumulative dose-limiting cardiac toxicity. Anthracyclines such as doxorubicin and daunorubicin cause acute toxic side effects, including bone marrow depression, alopecia, and stomatitis, and they are dose limited by a serious and mostly irreversible characteristic cardiomyopathy.35 The first study describing the encapsulation of anthracyclines into liposomes appeared in 1979. Work from various research groups followed soon after, supporting the general principle that liposomal formulations reduced the toxicity of anthracyclines in animal models.37
Dendrimer as a promising nanocarrier for the delivery of doxorubicin as an anticancer therapeutics
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Vanshikha Singh, Prashant Kesharwani
Nanomedicines of existing drugs can be used to overcome pharmaceutical problems such as lower solubility, systemic toxicity, bioavailability, immune-compatibility, and cellular uptake. Nanotechnology is therefore being implemented to deliver drug at its targeted site in controlled manner at the right place in right frequency, with improved patient safety, and reduced adverse effect. Some of the NPs formulated to deliver these anticancer drugs includes liposomes, polymeric NPs, lipid NPs, micellar NPs, and crystal NPs. Liposomal anticancer products like AmBisome (amphotericin B), Myocet (drug doxorubicin, DOX) for metastatic breast cancer, Doxil and Lipodox (drug DOX hydrochloride) for kaposki’s sarcoma, breast, and ovarian carcinoma, Visudyne (drug verteporfin), DaunoXome (for drug daunorubicin) for hemotological malignancy, and Onivyde (drug irinotecan) for metastatic pancreatic cancer are being marketed. Products under polymeric conjugates include Opaxio (Paclitaxel) for ovarian cancer and non-small cell lung cancer (NSCLC) in women, NKTR102 (PEG) (Irinotecan) for metastatic breast cancer, CRLX101 NP (Camptothecin) used for 3rd and 4th line renal cell carcinoma and 3rd line ovarian cancer and DEP™ (G5 PEG–Polylysine) (docetaxel) each of which is in different phases of clinical trials. Furthermore, nano micelle approved product includes Genexol-PM (paclitaxel) for breast cancer, NSCLC, and ovarian cancer therapy. Nanoxel and NK105 nanocarriers are other such nanoformulation for which studies are still under trials [21,22].
Functionalization of bioactive substrates with a F5SCH = CH moiety
Published in Journal of Sulfur Chemistry, 2020
Valery K. Brel, Oleg I. Artyushin, Aleksandra A. Moiseeva, Elena V. Sharova, Anastasiya G. Buyanovskaya, Yulia V. Nelyubina
A convenient approach to functionalize bioactive natural substrates with the pentafluorosulfanylvinyl moiety has been developed. Carbonates based on (pentafluoro-λ6-sulfanyl)alken-1-ols were shown to react readily with aliphatic amines as well as with an anthracycline antibiotic daunorubicin. Conjugates of pentafluorosulfanylvinyl derivatives and the alkaloid cytisine or antiviral drug camphocene were synthesized using click chemistry methodology. Studies of biological activeities of the pentafluorosulfanyl-substituted conjugates are in progress and will be reported in further publications.