Emergence of multi-drug resistance in fungal pathogens: a potential threat to fungicide performance in agriculture.

: 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.

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4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666201102121606 ◽

2020 ◽

Vol 20 ◽

Author(s):

Katharigatta N. Venugopala ◽

Christophe Tratrat ◽

Melendhran Pillay ◽

Pran Kishore Deb ◽

Deepak Chopra ◽

...

Keyword(s):

Drug Resistance ◽

Acyl Carrier Protein ◽

Phenyl Group ◽

Antitubercular Activity ◽

Docking Study ◽

Benzyl Ester ◽

Multi Drug Resistance ◽

Carrier Protein ◽

Molecular Docking Study ◽

Lipinski’S Rule

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB). Materials and Methods: Herein, the screening of a total of eight symmetrical 1,4-dihydropyridine (1,4-DHP) derivatives (4a-4h) was carried out for whole-cell anti-TB activity against the susceptible H37Rv and MDR strains of MTB. Results and Discussion: Most of the compounds exhibited moderate to excellent activity against the susceptible H37Rv. Moreover, the most promising compound 4f (against H37Rv) having para-trifluoromethyl phenyl group at 4-position and bis para-methoxy benzyl ester group at 3- and 5-positions of 1,4-dihydropyridine pharmacophore, exhibited no toxicity, but demonstrated weak activity against MTB strains resistant to isoniazid and rifampicin. In light of the inhibitory profile of the title compounds, enoyl-acyl carrier protein reductase (InhA) appeared to be the appropriate molecular target. Docking study of these derivatives against InhA receptor revealed favorable binding interactions. Further, in silico predicted ADME properties of these compounds 4a-4h were found to be in the acceptable ranges including satisfactory Lipinski’s rule of five, thereby indicating their potential as drug-like molecules. Conclusion: In particular, the 1,4-DHP derivative 4f can be considered as an attractive lead molecule for further exploration and development of more potent anti-TB agents as InhA inhibitors.

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Reversal of Multi-Drug Resistance in Staphylococcus aureus by Natural Product-Way Forward

Letters in Drug Design & Discovery ◽

10.2174/1570180813666151117212606 ◽

2016 ◽

Vol 13 (7) ◽

pp. 668-675

Author(s):

Saba Farooq ◽

. Atia-tul-Wahab ◽

Ali Azarpira ◽

. Atta-ur-Rahman ◽

M. Iqbal Choudhary

Keyword(s):

Staphylococcus Aureus ◽

Drug Resistance ◽

Natural Product ◽

Multi Drug Resistance

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Recent Development of Sulfonyl or Sulfonamide Hybrids as Potential Anticancer Agents: A Key Review

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171103140749 ◽

2018 ◽

Vol 18 (4) ◽

pp. 488-505 ◽

Cited By ~ 32

Author(s):

K. P. Rakesh ◽

Shi-Meng Wang ◽

Jing Leng ◽

L. Ravindar ◽

Abdullah M. Asiri ◽

...

Keyword(s):

Drug Resistance ◽

Anticancer Agents ◽

Side Effect ◽

Docking Studies ◽

Multi Drug Resistance ◽

Anticancer Activities ◽

Pharmacological Activities ◽

Synthetic Compounds ◽

Structure Activity ◽

Anticancer Drug Discovery

Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer drugs and diverse new natural or synthetic compounds are developed continuously by scientists. Presently, a large number of drugs in clinical practice have showed pervasive side effect and multidrug resistance. Sulfonyl or sulfonamide hybrids became one of the most attractive subjects due to their broad spectrum of pharmacological activities. Sulfonyl hybrids were broadly explored for their anticancer activities and it was found that they possess minimum side effect along with multi-drug resistance activity. This review describes the most recent applications of sulfonyl hybrid analogues in anticancer drug discovery and further discusses the mechanistic insights, structure-activity relationships and molecular docking studies for the potent derivatives.

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