scholarly journals Repurposing of FDA-Approved drugs to predict new inhibitors against key regulatory genes in Mycobacterium Tuberculosis

BIOCELL ◽  
2021 ◽  
Vol 45 (6) ◽  
pp. 1569-1583
Author(s):  
XINJUN YANG ◽  
AFTAB ALAM ◽  
NAIYAR IQBAL ◽  
KHALID RAZA
2021 ◽  
Vol 11 (6) ◽  
pp. 14688-14696

Tuberculosis (TB) is one of the most dreadful and deadliest diseases, killing millions annually. Its causative organism is a bacterium called Mycobacterium tuberculosis which primarily attacks the lungs. Tuberculosis can be classified as latent and active based on the presence/absence of the clinical manifestations. Also known as active TB, pulmonary TB is characterized by extreme infection, whereas in latent TB, no infection or symptom is seen. In this in silico study, we focus on the molecular docking-based virtual screening of 10 FDA-approved drugs which already used to treat bacterial infections against target methoxy mycolic acid synthase 4 (MMA4) and cyclopropane mycolic acid synthase (CmaA2). Drug-resistant TB is the most challenging factor for the design and formulation of anti-tuberculosis drugs. Mycolic acid plays a crucial role in the pathogenesis of TB and, therefore, can be an extremely valuable target. Based on a study conducted on mice, by rendering the hma genes (MMA4 and cmaA) inactive, no synthesis of mycolic acid is observed. The binding energy scores of each ligand docked against the target shows the affinity that happens against the Tuberculosis disease.


2015 ◽  
Vol 11 (12) ◽  
pp. 3316-3331 ◽  
Author(s):  
Gayatri Ramakrishnan ◽  
Nagasuma R. Chandra ◽  
Narayanaswamy Srinivasan

Drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery.


2019 ◽  
Vol 38 (9) ◽  
pp. 2521-2532 ◽  
Author(s):  
Jyoti Rani ◽  
Yumnam Silla ◽  
Kasmika Borah ◽  
Srinivasan Ramachandran ◽  
Urmi Bajpai

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
H Houson ◽  
J Schlesser ◽  
J Beverage ◽  
V Macherla ◽  
E Esquenazi

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.


2018 ◽  
Vol 15 (2) ◽  
pp. 208-220 ◽  
Author(s):  
Vaibhav Mishra ◽  
Tejpal Singh Chundawat

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.


2018 ◽  
Vol 14 (2) ◽  
pp. 106-116 ◽  
Author(s):  
Olujide O. Olubiyi ◽  
Maryam O. Olagunju ◽  
James O. Oni ◽  
Abidemi O. Olubiyi

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