Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs

Araújo, Renan Vinícius de; Santos, Soraya da Silva; Sanches, Luccas Missfeldt; Giarolla, Jeanine; Seoud, Omar A. El; Ferreira, Elizabeth Igne

doi:10.1590/0074-02760200229

Cited by 8 publications

(9 citation statements)

References 150 publications

(245 reference statements)

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“…Populations that live in conditions of vulnerability, such as lack of access to proper nutrition, sanitation and basic health care, are the ones at higher risk of acquiring these diseases. In fact, high incidences of both malaria and TB occur in several low-income countries ( de Araujo et al., 2020 ), in which cases of coinfection with both Plasmodium and M. tuberculosis must be common, although, probably, sub notification of such cases must occur.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria

Matteucci

Correa

Costa

2022

Front. Cell. Infect. Microbiol.

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Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, and malaria, caused by parasites from the Plasmodium genus, are two of the major causes of death due to infectious diseases in the world. Both diseases are treatable with drugs that have microbicidal properties against each of the etiologic agents. However, problems related to treatment compliance by patients and emergence of drug resistant microorganisms have been a major problem for combating TB and malaria. This factor is further complicated by the absence of highly effective vaccines that can prevent the infection with either M. tuberculosis or Plasmodium. However, certain host biological processes have been found to play a role in the promotion of infection or in the pathogenesis of each disease. These processes can be targeted by host-directed therapies (HDTs), which can be administered in conjunction with the standard drug treatments for each pathogen, aiming to accelerate their elimination or to minimize detrimental side effects resulting from exacerbated inflammation. In this review we discuss potential new targets for the development of HDTs revealed by recent advances in the knowledge of host-pathogen interaction biology, and present an overview of strategies that have been tested in vivo, either in experimental models or in patients.

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Section: Discussionmentioning

confidence: 99%

Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria

Matteucci

Correa

Costa

2022

Front. Cell. Infect. Microbiol.

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“…This is followed by Line probe assay (LPA), which can detect resistance to R, H, and particularly FQ and second-line injectables (SLI) drugs. [21] After assessing the efficacy and safety of the drugs and recommendations, WHO in its Consolidated Guidelines for TB Module 4: Treatment of Drug Resistant TB (2020), classified the second-line anti-TB drugs for the treatment of DR-TB into three groups:…”

Section: Drug Resistant-tb and Chemotherapymentioning

confidence: 99%

“…[22] Although there are predefined regimens for the chemotherapy of TB, still globally it's a huge challenge for the health system to manage TB patients. [23] WHO has provided various regimens for the treatment of DR-TB which are also being followed by the National Tuberculosis Elimination Programme (NTEP) of India. It includes a shorter oral Bdq-containing MDR/RR-TB regimen and a longer oral MDR/XDR-TB regimen.…”

Section: Drug Resistant-tb and Chemotherapymentioning

confidence: 99%

Novel Approaches for the Treatment of Drug-Resistant Tuberculosis

Pushkar¹,

Varshney²,

Pushkar³

et al. 2023

Pharmacogn. Res.

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Tuberculosis (TB) is a leading infectious disease that caused the deaths of a total of 1.5 million people in 2020 and is one of the top causes of death globally. India is a country with the highest TB burden, and it may affect all age groups. It is caused by the Mycobacterium tuberculosis bacteria, an intracellular pathogen, and its multidrug and extensively drug-resistant strains, which continue to emerge and spread, resulting in the deadliest infectious disease. After a gap of more than 40 years, the FDA approvals over the past decade of three second-line anti-TB drugs, bedaquiline, delamanid, and pretomanid, have been major forward steps in the management of drug-resistant-TB (DR-TB). Many medicinal plants such as Zanthoxylum leprieurii, Lantana camara, and Cryptolepis sanguinolenta have extensive therapeutic potential and represent a prospective option to fight against DR-TB. Some novel compounds are in the early clinical trial phases such as DprE1 inhibitors TBA-7371 and BTZ-043, and many others that are showing promising futures. This review describes DR-TB and its current chemotherapy guidelines including novel and repurposed drugs that are included in the anti-TB regimens, medicinal plants that have therapeutic potential for the development of drug-hit candidates, drugs that are currently in clinical development, host-directed therapy, and new drug delivery systems to better understand the novel therapeutic approaches that are currently being studied for the efficacious and safe management of DR-TB, a worldwide health problem.

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“…Malaria is an infectious disease caused by protozoa of the genus Plasmodium spp., and remains one of the major public health problems worldwide [ 1 ]. A total of 241 million cases and approximately 627,000 deaths were reported in 2020.…”

Section: Introductionmentioning

confidence: 99%

“…The current therapeutic arsenal for malaria is limited and the emergence of in vitro and in vivo cases of resistance for ACTs makes the search for new options for compounds that can be used in clinical practice even more necessary [ 1 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives

et al. 2022

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N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 μM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria. Graphical Abstract

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Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs

Cited by 8 publications

References 150 publications

Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria

Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria

Novel Approaches for the Treatment of Drug-Resistant Tuberculosis

Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives

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