Abstract:Graphical abstract
Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential f… Show more
“…7 a). Biologically divergent 1,2,4-oxadiazole derivative ( 8 ) [ 55 ] has been tightly accommodated with several solvent molecules and surrounded by amino acid residues in the active site of spike glycoprotein (Fig. 7 b).…”
In the absence of efficient anti-viral medications, the coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), has spawned a worldwide catastrophe and global emergency. Amidst several anti-viral targets of COVID-19, spike glycoprotein has been recognized as an essential target for the viral entry into the host cell. In the search of effective SARS CoV-2 inhibitors acting against spike glycoprotein, the virtual screening of 175,851 ligands from the 2020.1 Asinex BioDesign library has been performed using in silico tools like SiteMap analysis, pharmacophore-based screening, molecular docking using different levels of precision, such as high throughput virtual screening, standard precision and extra precision, followed by absorption, distribution, metabolism, excretion and toxicity analysis, and molecular dynamics (MD) simulation. Following a molecular docking study, seventeen molecules (with a docking score of less than − 6.0) were identified having the substantial interactions with the catalytic amino acid and nucleic acid residues of spike glycoprotein at the binding site. In investigations using MD simulations for 10 ns, the hit molecules (
1
and
2
) showed adequate compactness and uniqueness, as well as satisfactory stability. These computational research findings have offered a key starting point in the field of design and development of novel SARS CoV-2 entry inhibitors with appropriate drug likeliness.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s11030-022-10394-9.
“…7 a). Biologically divergent 1,2,4-oxadiazole derivative ( 8 ) [ 55 ] has been tightly accommodated with several solvent molecules and surrounded by amino acid residues in the active site of spike glycoprotein (Fig. 7 b).…”
In the absence of efficient anti-viral medications, the coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), has spawned a worldwide catastrophe and global emergency. Amidst several anti-viral targets of COVID-19, spike glycoprotein has been recognized as an essential target for the viral entry into the host cell. In the search of effective SARS CoV-2 inhibitors acting against spike glycoprotein, the virtual screening of 175,851 ligands from the 2020.1 Asinex BioDesign library has been performed using in silico tools like SiteMap analysis, pharmacophore-based screening, molecular docking using different levels of precision, such as high throughput virtual screening, standard precision and extra precision, followed by absorption, distribution, metabolism, excretion and toxicity analysis, and molecular dynamics (MD) simulation. Following a molecular docking study, seventeen molecules (with a docking score of less than − 6.0) were identified having the substantial interactions with the catalytic amino acid and nucleic acid residues of spike glycoprotein at the binding site. In investigations using MD simulations for 10 ns, the hit molecules (
1
and
2
) showed adequate compactness and uniqueness, as well as satisfactory stability. These computational research findings have offered a key starting point in the field of design and development of novel SARS CoV-2 entry inhibitors with appropriate drug likeliness.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s11030-022-10394-9.
“…Last decade has witnessed a paradigm shift in the way molecules are being synthesized specially the Ncontaining heterocycles. [3][4][5][42][43][44] In order to address some of the most burning questions of 21 st century i. e., the climate change and environment degradation, all domains of science and research have resorted to greener and sustainable protocols. Therefore into this pursuit, it is highly imperative to adapt to environmentally benign approaches for the synthesis of bioactive heterocycles.…”
Section: Sustainable Methods For Synthesis Of Quinolinesmentioning
confidence: 99%
“…Their prevalence could be understood with the fact that approximately ∼ 60 % of heterocycles amongst the drug candidate molecules possess nitrogen as heteroatom. [1,2] Some of the important N-containing heterocycles are indole, oxadiazole, pyrrole, quinoline, pyridine, quinazoline and quinoxaline [3][4][5][6] so on and so forth. These Ncontaining heterocycles found to possess broad spectrum of biological activities and are therefore considered as a most privileged class of biologically active chemical class utilized in medicinal chemistry (Figure 1).…”
Greener and sustainable synthetic strategies have been evolving as the demanding domain of organic transformations during the last decade. The division of an environmentally benign methodology to construct bioactive heterocyclic scaffolds has always been a perpetual subject of interests for medicinal and synthetic chemists. Thus, the newer and novel synthetic methodologies of quinoline have drawn the attention of synthetic organic or medicinal chemists as evident from the growing numbers of publications. The current review focuses on some of the notable synthetic methodologies carried out in the last decade with the inherent objective to attain sustainability towards the synthesis. The key aspects of the review would include to highlight sustainable and environmentally benign approaches like the solvent‐free reactions, use of alternate reaction media (e. g., water, fluorous alcohols, polyethylene glycols, and ionic liquids), and alternate modes of synthesis such as microwave‐assisted synthesis and flow reactions, nano‐catalysts, etc.
“…[18] On the another part, the innovative and green synthetic strategies have given a new era of synthesis of diversely substituted heterocycles. [19][20][21] Towards the on-going research endeveour on anti-TB agents, [22][23][24][25][26][27][28][29] recently we have reported the quinquennial account of diverse scaffolds in search of agents having anti-TB profile reported during 2016-2020. [30] In this review, we have shed light on candidates having anti-TB activity (minimum inhibitory concentration, MIC or hald maximal inhibitory concentrationm IC 50 of 20 μg/mL or μM) reported during 2021 retrieved through Sci-Finder [31] to educate the reader of the present work to update with the on-going trends on design of newly identified anti-tubercular agents.…”
Section: Diverse Scaffolds Reported For Anti-tb Activitymentioning
Tuberculosis (TB) has been the highly contagious airborne disease caused by Mycobacterium tuberculosis and the major leading infectious disease with the higher upsurge of morbidity and mortality. Owing to problems in the current regimen for TB and emergence of drug resistance strains, there is a strong necessity for development of new anti-TB drugs with better efficacy, reduced duration of action, along with improved patient compliance. Towards this, the scaffolds reported in 2021 with anti-tubercular activity such as benzofuran, benzothiazinone, benzimidazoles, indole, piperidine, piperazine, pyrazole, pyridine, pyrimidine, pyrrolidine, quinoxaline, triazole, etc. have been critically reviewed along with their structureactivity relationships, mode of actions with anticipations of intuitions to design the newer anti-mycobacterial scaffolds.The present work provide the organized coverage of diversified scaffolds with anti-tubercular profile reported in 2021 along with the insightful discussion on their merits and demerits. The mode of anti-tubercular action against Mycobacterium tuberculosis strains have been presented keeping in mind the novel drug candidates against drug resistant strains [a] Dr.
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