The first protein ever synthesized in vitro—a personal reminiscence of the total synthesis of crystalline insulin

2010 ◽  
Vol 53 (1) ◽  
pp. 16-18 ◽  
Author(s):  
YouShang Zhang
2019 ◽  
Vol 16 (3) ◽  
pp. 245-248
Author(s):  
Hummera Rafique ◽  
Aamer Saeed ◽  
Ehsan Ullah Mughal ◽  
Muhammad Naveed Zafar ◽  
Amara Mumtaz ◽  
...  

Background: (±)-6,8-Dihydroxy-3-undecyl-3,4-dihydroisochromen-1-one is one of the structural analog of several substituted undecylisocoumarins isolated from Ononis natrix (Fabaceae), has been successfully synthesized by direct condensation of homopthalic acid (1) with undecanoyl chloride yields isochromen-1-one (2). Methods: Alkaline hydrolysis of (2) gave the corresponding keto-acid (3), which is then reduced to hydroxy acid (4) then its cyclodehydration was carried out with acetic anhydride to afford 3,4- dihydroisochromen-1-one (5). Followed by demethylation step, the synthesis of target 6,8- dihydroxy-7-methyl-3-undecyl-3,4-dihydroisocoumarin (6) was achieved. Results: In vitro antibacterial screening of all the synthesized compounds were carried out against ten bacterial strains by agar well diffusion method. Conclusion: Newly synthesized molecules exhibited moderate antibacterial activity and maximum inhibition was observed against Bacillus subtilus and Salmonella paratyphi.


2021 ◽  
Vol 118 (9) ◽  
pp. e2021847118
Author(s):  
Susan Matthew ◽  
Qi-Yin Chen ◽  
Ranjala Ratnayake ◽  
Charles S. Fermaintt ◽  
Daniel Lucena-Agell ◽  
...  

Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin−GB1 complex.


2016 ◽  
Vol 30 (2) ◽  
pp. 35-42
Author(s):  
Durga Prasad Pandey ◽  
Hari Datta Bhattarai

Ramalin, a new L-glutamic acid derivative of phenylhydrazide (Y-glutamyl-N'-(2-hydroxyphenyl) hydrazide, 1) was isolated from the Antarctic lichen, Ramalina terebrata after a series of bioactivity guided fractionation of crude aqueous methanolic extract. Ramalin showed stronger antioxidant activities than commercially available standards, ascorbic acid, trolox, BHA, kojic acid in both, in vitro and in vivo test systems. In addition, ramalin showed no/less toxicity effects against two human cell lines; fibroblast (CCD-986SK) cells and keratinocyte (HaCaT). Thus, realign merits for cosmetic application and industrial scale production were needed. We developed a cost effective total synthesis of ramalin with 71.5% yield and described here.


2009 ◽  
Vol 81 (6) ◽  
pp. 1085-1091 ◽  
Author(s):  
Stephen Hanessian

X-ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has led to the design and synthesis of truncated and hydrid molecules exhibiting excellent inhibition in vitro. The design element has also been extended to the synthesis and in vitro inhibition of a series of achiral molecules deploying aromatic and heterocyclic core motifs with appropriately functionalized appendages that provide excellent binding interactions at the S1, S2, and S3 sites of thrombin. Excellent selectivity for thrombin over trypsin has also been observed. Thus, studies in total synthesis of highly active natural aeruginosins have inspired further work toward truncated and hybrid analogs with excellent inhibitory activities. Structure-based organic synthesis has guided our research from natural products toward unnatural drug-like prototypes.


2016 ◽  
Vol 120 ◽  
pp. 86-96 ◽  
Author(s):  
T. Vijai Kumar Reddy ◽  
A. Jyotsna ◽  
B.L.A. Prabhavathi Devi ◽  
R.B.N. Prasad ◽  
Y. Poornachandra ◽  
...  

ChemInform ◽  
2006 ◽  
Vol 37 (3) ◽  
Author(s):  
Nestor M. Carballeira ◽  
David Sanabria ◽  
Keykavous Parang

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 661
Author(s):  
Irene Torres-García ◽  
Josefa L. López-Martínez ◽  
Manuel Muñoz-Dorado ◽  
Ignacio Rodríguez-García ◽  
Miriam Álvarez-Corral

Organic extracts of marine invertebrates, mainly sponges, from seas all over the world are well known for their high in vitro anticancer and antibiotic activities which make them promising sources of compounds with potential use as pharmaceutical leads. Most of the structures discovered so far have a peculiar structural feature in common: a 1,2-dioxane ring. This is a highly reactive heterocycle that can be considered as an endoperoxide function. Together with other structural features, this group could be responsible for the strong biological activities of the substances present in the extracts. Numerous research programs have focused on their structural elucidation and total synthesis since the seventies. As a consequence, the number of established chiral centres and the similarity between different naturally occurring substances is increasingly higher. Most of these compounds have a terpenoid nature, mainly diterpene and sesterterpene, with several peculiar structural features, such as the loss of one carbon atom. Although there are many reviews dealing with the occurrence of marine peroxides, their activities, or potential pharmaceutical uses, no one has focused on those having a terpene origin and the endoperoxide function. We present here a comprehensive review of these compounds paying special attention to their structural features and their biological activity.


Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 93 ◽  
Author(s):  
Sofia-Eléna Motuhi ◽  
Omid Feizbakhsh ◽  
Béatrice Foll-Josselin ◽  
Blandine Baratte ◽  
Claire Delehouzé ◽  
...  

The marine α-pyrone macrolide neurymenolide A was previously isolated from the Fijian red macroalga, Neurymenia fraxinifolia, and characterized as an antibacterial agent against antibiotic-resistant strains that also exhibited moderate cytotoxicity in vitro against cancer cell lines. This compound was also shown to exhibit allelopathic effects on Scleractinian corals. However, to date no mechanism of action has been described in the literature. The present study showed, for the first time, the isolation of neurymenolide A from the New Caledonian Rhodophyta, Phacelocarpus neurymenioides. We confirmed the compound’s moderate cytotoxicity in vitro against several human cell lines, including solid and hematological malignancies. Furthermore, we combined fluorescence microscopy and flow cytometry to demonstrate that treatment of U-2 OS osteosarcoma human cells with neurymenolide A could block cell division in prometaphase by inhibiting the correct formation of the mitotic spindle, which induced a mitotic catastrophe that led to necrosis and apoptosis. Absolute configuration of the stereogenic center C-17 of neurymenolide A was deduced by comparison of the experimental and theoretical circular dichroism spectra. Since the total synthesis of this compound has already been described, our findings open new avenues in cancer treatment for this class of marine molecules, including a new source for the natural product.


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