3D Atom based QSAR model of DprE1 inhibitors as Anti-tubercular Agents

2021 ◽  
pp. 5903-5910
Author(s):  
K Poojita ◽  
Fajeelath Fathima ◽  
Rajdeep Ray ◽  
Lalit Kumar ◽  
Ruchi Verma
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mortality Rate ◽  
3D Qsar ◽  
Qsar Model ◽  
New Novel ◽  
Novel Drugs ◽  
Mdr Tb ◽  
The Stability ◽  
Derivatives Of ◽  
Tuberculosis Disease

Tuberculosis disease is world’s biggest threat to health with a high mortality rate. There has been a steady surge in the frequency of MDR-TB and XDR-TB. Hence, it is imperative to encourage the research and development of novel drugs to counteract the infection. Decaprenylphosphoryl-ß-D-ribose-2'α-epimerase 1 (DprE1) is a valuable enzyme which is responsible for the stability and virulence of the infection causing bacteria (Mycobacterium tuberculosis) thereby making it a perfect target for drugs anti TB activity. This study represent atom based 3D QSAR model consisting the derivatives of DprE1 inhibitors and provides guidance and insight to develop and identify new novel molecule which have good therapeutic efficiency as Anti TB drugs.

scholarly journals Bioprospecting for antituberculosis natural products – A review

2021 ◽  
Vol 19 (1) ◽  
pp. 1074-1088
Author(s):  
Olabisi Flora Davies-Bolorunduro ◽  
Abraham Ajayi ◽  
Isaac Adeyemi Adeleye ◽  
Alfinda Novi Kristanti ◽  
Nanik Siti Aminah
Keyword(s):  
Natural Products ◽  
Mycobacterium Tuberculosis ◽  
High Throughput Screening ◽  
Antitubercular Drug ◽  
Natural Sources ◽  
Resource Limited ◽  
Novel Drugs ◽  
Mdr Tb ◽  
Drug Leads ◽  
Novel Antibiotics

Abstract There has been an increase in the reported cases of tuberculosis, a disease caused by Mycobacterium tuberculosis, which is still currently affecting most of the world’s population, especially in resource-limited countries. The search for novel antitubercular chemotherapeutics from underexplored natural sources is therefore of paramount importance. The renewed interest in studies related to natural products, driven partly by the growing incidence of MDR-TB, has increased the prospects of discovering new antitubercular drug leads. This is because most of the currently available chemotherapeutics such as rifampicin and capreomycin used in the treatment of TB were derived from natural products, which are proven to be an abundant source of novel drugs used to treat many diseases. To meet the global need for novel antibiotics from natural sources, various strategies for high-throughput screening have been designed and implemented. This review highlights the current antitubercular drug discovery strategies from natural sources.

scholarly journals Calculation of the Stability of the IS6110 Banding Pattern in Patients with Persistent Mycobacterium tuberculosis Disease

2002 ◽  
Vol 40 (5) ◽  
pp. 1705-1708 ◽  
Author(s):  
R. M. Warren ◽  
G. D. van der Spuy ◽  
M. Richardson ◽  
N. Beyers ◽  
M. W. Borgdorff ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Banding Pattern ◽  
The Stability ◽  
Tuberculosis Disease

scholarly journals Review of the Effectiveness of Various Adjuvant Therapies in Treating Mycobacterium tuberculosis

2021 ◽  
Vol 13 (3) ◽  
pp. 821-834
Author(s):  
Arman Amin ◽  
Artin Vartanian ◽  
Aram Yegiazaryan ◽  
Abdul Latif Al-Kassir ◽  
Vishwanath Venketaraman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Online Databases ◽  
Mdr Tb ◽  
Tuberculosis Disease ◽  
Specific Search ◽  
Resistant Genotypes ◽  
Minimal Research

Tuberculosis disease is caused by the bacterium Mycobacterium tuberculosis. It is estimated that 10 million people have developed tuberculosis disease globally, leading to 1.4 million deaths in 2019. Treatment of tuberculosis has been especially challenging due to the rise of multidrug-resistant (MDR-TB) and extensive drug-resistant (XDR-TB) tuberculosis. In addition to drug-resistant genotypes, the standard treatment of tuberculosis by first-line agents is also challenging due to toxicity and costs. In the last four decades, there have only been two new anti-tuberculosis agents—bedaquiline and delamanid. Therefore, shorter, safer, and more cost-effective therapies are needed to adequately treat tuberculosis. In this review, we explore various adjuvants such as glutathione, everolimus, vitamin D, steroid, aspirin, statin, and metformin and their usefulness in reducing the burden of tuberculosis. Glutathione, everolimus, aspirin, and metformin showed the most promise in alleviating the burden of tuberculosis. Despite their potential, more clinical trials are needed to unequivocally establish the effectiveness of these adjuvants as future clinical therapies. Methods: The journals for this review were selected by conducting a search via PubMed, Google Scholar, and The Lancet. Our first search included keywords such as “tuberculosis” and “adjuvant therapy.” From the search, we made a list of adjuvants associated with tuberculosis, and this helped guide us with our second online database search. Using the same three online databases, we searched “tuberculosis” and “respective therapy.” The adjuvants included in the paper were selected based on the availability of sufficient research and support between the therapy and tuberculosis. Adjuvants with minimal research support were excluded. There were no specific search criteria regarding the timing of publication, with our citations ranging between 1979 to 2021.

Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Deepa Parwani ◽  
Sushanta Bhattacharya ◽  
Akash Rathore ◽  
Chaitali Mallick ◽  
Vivek Asati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multi Drug Resistance ◽  
Benzimidazole Derivatives ◽  
Duration Of Treatment ◽  
Structure Activity ◽  
Mdr Tb ◽  
Low Toxicity ◽  
Extensively Drug Resistance ◽  
Improved Characteristics

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

Generation of Pharmacophore and Atom Based 3D-QSAR Model of Novel Isoquinolin-1-one and Quinazolin-4-one-type Inhibitors of TNFα

2012 ◽  
Vol 8 (3) ◽  
pp. 436-451 ◽  
Author(s):  
Pradeep Hanumanthappa ◽  
Mahesh K. Teli ◽  
Rajanikant G. Krishnamurthy
Keyword(s):  
3D Qsar ◽  
Qsar Model

Binding of calcium and lead ions to carboxystarch prepared by action of nitrogen dioxide on native starch and its 2,3-dialdehyde derivatives

1986 ◽  
Vol 51 (6) ◽  
pp. 1340-1351 ◽  
Author(s):  
Rudolf Kohn ◽  
Karol Tihlárik
Keyword(s):  
Nitrogen Dioxide ◽  
Alkaline Medium ◽  
Binding Capacity ◽  
Lead Ions ◽  
Carbonyl Groups ◽  
Weakly Alkaline ◽  
Exchange Cations ◽  
Counter Ions ◽  
The Stability ◽  
Derivatives Of

The binding of calcium and lead ions to carboxy derivatives of starch prepared by allowing nitrogen dioxide to act on native maize starch (procedure A) and on starch 2,3-dialdehyde derivatives of degrees of oxidation DO(d.a.) ≥ 0.94 (procedure B) was studied. The carboxy group content of the samples in the H+ form was 4.6 - 12.1 mmol g-1. The effect of alkaline medium on the stability of the carboxy derivatives and on their ability to bind and exchange cations was examined. The Ca2+ → 2K+ exchange was evaluated in terms of the decrease in the electrostatic free enthalpy Δ(Gel/N)KCa, determined by alkalimetric potentiometric titrations, and the binding of Pb2+ ions was evaluated in terms of the activity of the Pb2+ counter-ions determined in suspensions of Pb salts of the carboxy derivatives by means of an ion specific electrode. The IR and CD spectra revealed that the carboxystarch preparations obtained by procedure A contained, in addition to free carboxy groups, a considerable amount of carbonyl groups. During the conversion of the latter groups to the former, even in a weakly alkaline medium, the carboxy derivatives undergo an appreciable degradation and lose, to a great extent, their ability to bind and exchange cations. Procedure B, on the other hand, leads to highly selective starch and amylose carboxy derivatives, exhibiting a small amount of carbonyl groups and featuring a relative stability towards alkaline medium; their binding capacity is as high as 12 milliequivalents of cations per g of sample.

scholarly journals Antioxidant Network Based on Sulfonated Polyhydroxyalkanoate and Tannic Acid Derivative

2021 ◽  
Vol 8 (1) ◽  
pp. 9
Author(s):  
Laura Brelle ◽  
Estelle Renard ◽  
Valerie Langlois
Keyword(s):  
Gallic Acid ◽  
Tannic Acid ◽  
Water Soluble ◽  
Gel Formation ◽  
Ene Reaction ◽  
Inorganic Cations ◽  
Medium Chain Length ◽  
Physically Crosslinked ◽  
The Stability ◽  
Derivatives Of

A novel generation of gels based on medium chain length poly(3-hydroxyalkanoate)s, mcl-PHAs, were developed by using ionic interactions. First, water soluble mcl-PHAs containing sulfonate groups were obtained by thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. Anionic PHAs were physically crosslinked by divalent inorganic cations Ca2+, Ba2+, Mg2+ or by ammonium derivatives of gallic acid GA-N(CH3)3+ or tannic acid TA-N(CH3)3+. The ammonium derivatives were designed through the chemical modification of gallic acid GA or tannic acid TA with glycidyl trimethyl ammonium chloride (GTMA). The results clearly demonstrated that the formation of the networks depends on the nature of the cations. A low viscoelastic network having an elastic around 40 Pa is formed in the presence of Ca2+. Although the gel formation is not possible in the presence of GA-N(CH3)3+, the mechanical properties increased in the presence of TA-N(CH3)3+ with an elastic modulus G’ around 4200 Pa. The PHOSO3−/TA-N(CH3)3+ gels having antioxidant activity, due to the presence of tannic acid, remained stable for at least 5 months. Thus, the stability of these novel networks based on PHA encourage their use in the development of active biomaterials.

scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

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