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Selected Green Efforts to Utilization of Carbohydrates
Published in Ahindra Nag, Greener Synthesis of Organic Compounds, Drugs and Natural Products, 2022
Oseltamivir (Tamiflu, Figure 13.1), approved by the FDA in 1999, has been one of the mainstay neuraminidase inhibitors against seasonal influenza and stockpiled also in view of pandemic influenza. Though a number of recent studies have questioned the risk–benefit ratio of this drug.31,32 More than 70 Tamiflu synthetic procedures have been developed in the past 20 years in order to achieve a significantly efficient, safe, cost-effective and environmentally benign synthetic procedure.33 (-)-shikimic acid was used as starting material and remains the current industrial synthetic starting material. The original synthesis of oseltamivir carboxylate proceeded in 15% overall yield over 14 synthetic steps despite using protecting group chemistry.34 The Roche approach led to a 12-step route starting from (-)-shikimic acid with an overall yield of ~35%,35 which went hand in hand with improved sourcing and purification of (-)-shikimic acid. A shorter (8 steps) approach toward Tamiflu with an improved 47% overall yield was developed by Shi et al.36 The overall yield improved slightly (35–47%) and the number of transformations was considerably reduced relative to the Roche industrial approach (12 steps to eight steps).35,36 This approach represents a model of atom economy since no protecting group manipulations were needed.
2D-QSAR, 3D-QSAR, molecular docking and ADMET prediction studies of some novel 2-((1H-indol-3-yl)thio)-N-phenyl-acetamide derivatives as anti-influenza A virus
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Mustapha Abdullahi, Adamu Uzairu, Gideon Adamu Shallangwa, Paul Andrew Mamza, Muhammad Tukur Ibrahim
Influenza (A) virus (IAV) infection remains one of the major causes of mortality and morbidity due to respiratory diseases in recent times even with the devastating Covid-19 pandemic [1]. The World Health Organization (WHO) reported about 2–5 million cases of severe illness caused by the ravaging seasonal influenza virus epidemic which resulted in over 500,000 deaths globally [2]. These flu epidemics cause severe respiratory infections in children, adults, the elderly, and individuals with underlying health conditions [3] [4]. Influenza virus neuraminidase (NA) is an enzyme that catalyzes the obliteration of terminal sialic acid residues (sialidase) which aids in liberating new virions formed from the infected cells and circulating to infect the neighboring cells [5]. As such, the NA inhibition can defend the host from being infected and prevent its proliferation [1]. Due to the highly preserved active site structure of neuraminidase [6], it has become an attractive molecular target for the exploration and development of novel anti-influenza inhibitors. Presently, Zanamivir (Relenza™), oseltamivir (Tamiflu™), laninamivir octanoate (Inavir™), and peramivir (Rapivab™) are the four (4) approved neuraminidase inhibitors for influenza treatment [7]. The IAV disease is usually linked to severe symptoms because of the intense genetic diversity characterized by chromosomal mutation between avian and human viruses. Presently, the only two major classes of antiviral medicines against the influenza A virus are inhibitors of M2-ion channel (rimantadine and amantadine) and neuraminidase (zanamivir and oseltamivir) targets that fight against its spreading around the globe. However, most influenza A virus strains have become resistant to these drugs in recent times. There is a lot of concern for the advent of drug resistance effects resulting from the high variability of the influenza virus or respiratory syncytial virus (RSV) [5]. This is because a patient infected with either virus can manifest similar symptoms at an early stage. The discovery of some novel compounds of 2-((1 H-indol-3-yl)thio) acetamide as dual inhibitors against IAV and RSV is a huge milestone for the rapid therapy of these respiratory co-infections. Moreover, the trial and error approach applied in the development of new drugs has been seen to be very tedious, costly, and time-consuming [8].