Integrated Approach to Nature as Source of New Drug Lead

Abstract Background Despite the various strategies undertaken in the clinical practice, the mortality rate due to antibiotic-resistant microbes has been markedly increasing worldwide. In addition to multidrug-resistant (MDR) microbes, the “ESKAPE” bacteria are also emerging. Of course, the infection caused by ESKAPE cannot be treated even with lethal doses of antibiotics. Now, the drug resistance is also more prevalent in antiviral, anticancer, antimalarial and antifungal chemotherapies. Main body To date, in the literature, the quantum of research reported on the discovery strategies for new antibiotics is remarkable but the milestone is still far away. Considering the need of the updated strategies and drug discovery approaches in the area of drug resistance among researchers, in this communication, we consolidated the insights pertaining to new drug development against drug-resistant microbes. It includes drug discovery void, gene paradox, transposon mutagenesis, vitamin biosynthesis inhibition, use of non-conventional media, host model, target through quorum sensing, genomic-chemical network, synthetic viability to targets, chemical versus biological space, combinational approach, photosensitization, antimicrobial peptides and transcriptome profiling. Furthermore, we optimally briefed about antievolution drugs, nanotheranostics and antimicrobial adjuvants and then followed by twelve selected new feasible drug targets for new drug design against drug resistance. Finally, we have also tabulated the chemical structures of potent molecules against antimicrobial resistance. Conclusion It is highly recommended to execute the anti-drug resistance research as integrated approach where both molecular and genetic research needs to be as integrative objective of drug discovery. This is time to accelerate new drug discovery research with advanced genetic approaches instead of conventional blind screening.

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An integrated approach to the selection of optimal salt form for a new drug candidate

International Journal of Pharmaceutics ◽

10.1016/0378-5173(94)90104-x ◽

1994 ◽

Vol 105 (3) ◽

pp. 209-217 ◽

Cited By ~ 97

Author(s):

Kenneth R. Morris ◽

Michael G. Fakes ◽

Ajit B. Thakur ◽

Ann W. Newman ◽

Ambarish K. Singh ◽

...

Keyword(s):

Integrated Approach ◽

Drug Candidate ◽

Salt Form ◽

New Drug ◽

Selection Of

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New drug lead from Madagascar's rainforests

Nature Reviews Microbiology ◽

10.1038/nrmicro1623 ◽

2007 ◽

Vol 5 (3) ◽

pp. 165-165

Author(s):

Alexandra Flemming

Keyword(s):

New Drug ◽

Drug Lead

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Ring Expansion to 8-Membered Silacycles via Formal Cross-Dimerization of 5-Membered Palladacycles with Silacyclobutanes

10.26434/chemrxiv.14510718.v1 ◽

2021 ◽

Author(s):

Xi-Chao Wang ◽

Hao-Ran Wang ◽

Xiufang Xu ◽

Dongbing Zhao

Keyword(s):

Ring Expansion ◽

Membered Ring ◽

Lead Compounds ◽

New Drug ◽

Drug Lead ◽

Important Significance

Investigations of the sila-8-membered ring fused biaryls are of important significance for the discovery of new drug lead compounds. However, such compounds are still unknown due to the synthetic challenge. Herein we describe the chemo- and regio-selective cross-dimerization of 5-membered palladacycles with silacyclobutanes enabled by Pd-catalytic conditions, which constitutes an expedient ring expansion route to the sila-8-membered ring fused biaryl skeletons.

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Diversity-Oriented Synthesis Yields a New Drug Lead for Treatment of Chagas Disease

ACS Medicinal Chemistry Letters ◽

10.1021/ml400403u ◽

2014 ◽

Vol 5 (2) ◽

pp. 149-153 ◽

Cited By ~ 32

Author(s):

Sivaraman Dandapani ◽

Andrew R. Germain ◽

Ivan Jewett ◽

Sebastian le Quement ◽

Jean-Charles Marie ◽

...

Keyword(s):

Chagas Disease ◽

Diversity Oriented Synthesis ◽

New Drug ◽

Drug Lead

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From Genome to Drugs: New Approaches in Antimicrobial Discovery

Frontiers in Pharmacology ◽

10.3389/fphar.2021.647060 ◽

2021 ◽

Vol 12 ◽

Author(s):

Federico Serral ◽

Florencia A. Castello ◽

Ezequiel J. Sosa ◽

Agustín M. Pardo ◽

Miranda Clara Palumbo ◽

...

Keyword(s):

Drug Discovery ◽

Target Selection ◽

Public Health Problem ◽

Private Investment ◽

Cost Effective ◽

Omics Data ◽

Bacterial Strains ◽

Compound Identification ◽

New Drug ◽

Drug Lead

Decades of successful use of antibiotics is currently challenged by the emergence of increasingly resistant bacterial strains. Novel drugs are urgently required but, in a scenario where private investment in the development of new antimicrobials is declining, efforts to combat drug-resistant infections become a worldwide public health problem. Reasons behind unsuccessful new antimicrobial development projects range from inadequate selection of the molecular targets to a lack of innovation. In this context, increasingly available omics data for multiple pathogens has created new drug discovery and development opportunities to fight infectious diseases. Identification of an appropriate molecular target is currently accepted as a critical step of the drug discovery process. Here, we review how diverse layers of multi-omics data in conjunction with structural/functional analysis and systems biology can be used to prioritize the best candidate proteins. Once the target is selected, virtual screening can be used as a robust methodology to explore molecular scaffolds that could act as inhibitors, guiding the development of new drug lead compounds. This review focuses on how the advent of omics and the development and application of bioinformatics strategies conduct a “big-data era” that improves target selection and lead compound identification in a cost-effective and shortened timeline.

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