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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
The two most common forms of vaginitis during pregnancy are fungal and protozoan. Pregnant women with vaginitis secondary to fungi, such as Candida species, can be treated with a variety of antifungal agents that are listed in Box 2.24. Women with trichomoniasis present an unusual therapeutic dilemma. Although there is no scientific evidence that metronidazole is either teratogenic or causes adverse effects in the embryo/fetus, the manufacturer has issued a stern warning regarding its use during the first trimester of pregnancy. Fortunately, many of the patients with trichomoniasis can be treated with antiprotozoal agents until they are past the first trimester and then treated with metronidazole—the only effective treatment for this protozoan infection.
Current Epidemiological and Clinical Features of COVID-19; a Global Perspective From China
Published in William C. Cockerham, Geoffrey B. Cockerham, The COVID-19 Reader, 2020
Huilan Tu, Sheng Tu, Shiqi Gao, Anwen Shao, Jifang Sheng
There are many other antiviral drugs with potential as treatment options against COVID-19. Remdesivir, a nucleotide analog prodrug currently in clinical trials for the treatment of Ebola virus infections,89 is a promising compound,90 since preclinical studies have suggested that remdesivir may be effective for both prophylaxis and treatment of HCoV infections.54,91,92 Elfiky93 found that sofosbuvir was a potent inhibitor of COVID-19 RNA-dependent RNA polymerase (RdRp). Oseltamivir is a neuraminidase inhibitor indicated for the treatment of influenza.94,95 Nafamostat can block MERS-CoV infection in vitro96 and is potentially applicable to the treatment of Ebola virus disease.97 Favipiravir is a broad-spectrum antiviral that has shown promise for treating influenza98 and may also be effective against the Ebola virus.99 Nitazoxanide is both an antiprotozoal agent and a first-in-class broad-spectrum antiviral agent100 that may be useful for the treatment of MERS infections.101
Curcumin and Neglected Infectious Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Francesca Mazzacuva, Agostino Cilibrizzi
In a different study, the antiparasitic effects of curcumin (1) were evaluated in combination with benznidazole (22) (Figure 6), a typical drug also used in Chagas disease chemotherapy (Novaes et al. 2016). In mice acutely infected with Trypanosoma cruzi, the co-administration of benznidazole (22) and curcumin (1) revealed a significant decrease of parasite load, circulating levels of cytokines (e.g., INF–γ and interleukin 4) and myocardial inflammation, with a parallel reduction of the overall parasitemia. The combined therapy showed exceeding effects of benznidazole (22) monotherapy. In this study, curcumin (1) demonstrated not only improvement of the efficacy of benznidazole (22) but, most relevant, the allowing of the reduction of its therapeutic dose with a significant decrease of the overall toxicity. Antiparasitic and antiprotozoal agents in clinical use to treat various neglected diseases, including African trypanosomiasis and leishmaniasis.
Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Heba A. S. El-Nashar, Ahmed M. Sayed, Hany A. M. El-Sherief, Mostafa E. Rateb, Lina Akil, Ibrahim Khadra, Taghreed A. Majrashi, Sara T. Al-Rashood, Faizah A. Binjubair, Mahmoud A. El Hassab, Wagdy M. Eldehna, Usama Ramadan Abdelmohsen, Nada M. Mostafa
Trypanosomiasis or sleeping sickness is a protozoan disease that infects animals and humans transmitted by the bite of Glossina (tsetse) fly carrying Trypanosoma brucei1. Currently, trypanosomiasis affects more than 50 million cattle and 70 million people in sub-Saharan Africa2. The available current medicines record lack of efficiency, resistance, and toxicity, so there is an urgent need for the development of novel, safe, efficacious, cost-effective drugs with new mechanism of action3,4. In African countries where trypanosomiasis is prevalent, natural products (herbal extracts) have traditionally been utilised for centuries and are still extensively used to cure infections and other parasitic diseases5,6. Interestingly, about 30% of the world population has confidence in traditional therapies due to their wide availability and affordability7. Moreover, various drugs like quinine and artemisinin were established as plant-derived potential antiprotozoal agents8.
New pyrazolylpyrazoline derivatives as dual acting antimalarial-antileishamanial agents: synthesis, biological evaluation and molecular modelling simulations
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Adnan A. Bekhit, Eskedar T. Lodebo, Ariaya Hymete, Hanan M. Ragab, Salma A. Bekhit, Kikuko Amagase, Afnan Batubara, Mohammed A. S. Abourehab, Alaa El-Din A. Bekhit, Tamer M. Ibrahim
Leishmaniasis is a complex disease that is caused by more than 20 species of Leishmania and is correlated to several clinical manifestations ranging from simple skin lesions around the bite site to fatal visceral forms4,5. More than one billion people are at risk of leishmaniasis in endemic areas6,7. Therefore, there is a continuing necessity to discover new antiprotozoal agents that are effective against multidrug-resistant parasites and inhibitors that target enzymes and proteins macromolecules8,9. For the folate pathway, dihydrofolate Reductase (DHFR) and Pteridine reductase (PTR1) are validated targets for leishmania10. Their main role is to reduce oxidised pteridines like biopterin and folate to active cofactors tetrahydrobiopterin (THB) and tetrahydrofolate (THF), respectively. Nonetheless, utmost leishmania species showed resistance against DHFR-TS inhibitors11,12, owing to the presence of an alternative salvage pathway regulated by PTR1. Interestingly, the PTR1 enzyme is overexpressed in strains that exhibited antifolate resistance, hence, offering the means to bypass the dihydrofolate reductase-thymidylate synthase (DHFR-TS) pathway13–15.
Thio- and selenosemicarbazones as antiprotozoal agents against Trypanosoma cruzi and Trichomonas vaginalis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Alexandra Ibáñez-Escribano, Cristina Fonseca-Berzal, Mónica Martínez-Montiel, Manuel Álvarez-Márquez, María Gómez-Núñez, Manuel Lacueva-Arnedo, Teresa Espinosa-Buitrago, Tania Martín-Pérez, José Antonio Escario, Penélope Merino-Montiel, Sara Montiel-Smith, Alicia Gómez-Barrio, Óscar López, José G. Fernández-Bolaños
Management of diseases caused by pathogenic protozoa is not a simple task4. On the one hand, development of successful vaccines is a hitherto unachieved goal5; on the other hand, the chemotherapeutic arsenal available so far suffers from important drawbacks: most of them are old drugs that are developing chemoresistance6, and are endowed with severe side-effects7 and low efficiency8. Moreover, their high prices, and complex administration protocols make them unaffordable for underdeveloped countries9. Accordingly, the development of new antiprotozoal agents is a hot topic in current Medicinal Chemistry research10,11.