China
Africa
Explore chapters and articles related to this topic
Abies Spectabilis (D. Don) G. Don (Syn. A. Webbiana Lindl.) Family: Coniferae
Published in L.D. Kapoor, Handbook of Ayurvedic Medicinal Plants, 2017
Pharmacological action — Bark is bitter, stomachic, astringent, powerful antidysenteric, febrifuge, and anthelmintic. Seeds are very bitter, astringent, febrifuge, antidysenteric, anthalmintic, carminative, and also antiperiodic in combination with other antiperiodics. The therapeutic utility of kurchi in acute and chronic amebic dysentery has been well known. Various fractions of H. antidysenterica showed promising activity against experimental amebiasis in rats and hamsters. Conessine was more potent as an amebicidal agent in vitro than the other alkaloids of the plant, viz., conessidine deydrate, conkurchine, holarrhine, and kurchicine.450
Steroidal Alkaloids
Published in Amritpal Singh Saroya, Contemporary Phytomedicines, 2017
Conessine (Fig. 21.3) is a steroid alkaloid found in Holarrhenafloribunda (L.) Wall. (Duez et al. 1987), Holarrhena antidysenterica (L.) Wall. (Dohnal et al. 1990; Kumar et al. 2007) and Funtumia elastica (Preuss) Stapf. (Zirihi et al. 2005).
Drug Discovery: From Hits to Clinical Candidates
Published in Divya Vohora, The Third Histamine Receptor, 2008
Sylvain Celanire, Florence Lebon, Holger Stark
Also from a marine sponge of Verongidae family, Aplysina sp., aplysamine-1 (4) has been detected as a moderate potent antagonist and one of the first nonimidazole compounds (Figure 5.4) [20]. Later investigations on structure-activity relationships (SAR) demonstrate that the related debromo tyramine-based derivative is about five times more potent than 4 (pKi 8.2 versus 7.5, respectively) [21]. One of the most interesting findings in natural products is the detection of the azacyclosteroid conessine (5) as potent (pKi 8.3), and brain-penetrating histamine H3R antagonist by high-throughput screening (HTS) from Abbott Labs [22–24]. This alkaloid does not possess any aromatic moiety and demonstrates a strict geometry of functionalities. Therefore, it is an excellent tool for computational models. The importance of both basic centers was investigated by amide (ring E, 6, pKi 6.3) or carbamate formation (exocyclic N-containing functionality, 7, pKi 7.7). Different carbamate, amide, amine, alcohol, ester, ether, ketone, and alkene derivatives are described related to the variation on compound 8. Further derivative (9) containing aromatic A and B rings were also allowed, maintaining H3R affinity (pKi 9.9-6.1). Synthetic approaches to such compounds are described by Kopach et al. [25] and Jiang and Xu [26]. The reason for broad variations of the amino functionality was based on the poor pharmacokinetic properties of conessine (5). Although it showed a high brain/blood concentration ratio, its extremely low central nervous system (CNS) clearance, low selectivity versus α2-adrenoceptors (pKi 8.0), and potential to induce phospholipidosis (probably due to its cationic amphiphilic feature) were the most important drawbacks [27, 28]. Recently, conessine has also been isolated from the stem bark of African Funtumia elastica, Apocynaceae, and showed moderate antiplasmodial activity [29]. The utility of natural products as sources of novel structures is well known although they will not necessarily be the final drug entity [30].
Efflux in Gram-negative bacteria: what are the latest opportunities for drug discovery?
Published in Expert Opinion on Drug Discovery, 2023
Teresa Gil-Gil, Pablo Laborda, Luz Edith Ochoa-Sánchez, José Luis Martínez, Sara Hernando-Amado
Given the clinical relevance of P. aeruginosa, different works, analyzing potential inhibitors of its efflux pumps, have been published. Lanatoside C, diadzein, conessine, curcumine, berberine, and palmatine from Digitalis lanata, Glycine max, Curcuma longa, Holarrhena antidysenterica, and Berveris bulgaris, respectively [147,151–153], are inhibitors of the intrinsic resistance element MexAB-OprM [41]. Diadzein and Lanatoside C also have inhibitory activity against the AcrAB-TolC efflux pump of E. coli [147]. In addition, the activity of this efflux pump is inhibited by ursolic acid from Eucalyptus tereticornis [149], lysergol from Ipomea muricata [148], gallotannin 1,2,6-tri-O-galloyl-β-d-glucopyranose from Terminalia chebula [150], 4-hydroxy-ά-tetralone combined with its semisynthetic derivatives from Ammannia spp. [154] and plumbagin, nordihydroguaretic acid and shikonin from Plumbago indica, Larrea tridentata, and Lithospermum erythrorhizon, respectively [155]. Altogether, these data indicate that phenolic and aromatic compounds, flavones, alkaloids, or tannins from plants are valuable sources of efflux pump inhibitors.
The development of efflux pump inhibitors to treat Gram-negative infections
Published in Expert Opinion on Drug Discovery, 2018
Paula Blanco, Fernando Sanz-García, Sara Hernando-Amado, José Luis Martínez, Manuel Alcalde-Rico
Some of the EPIs so far described are phenolic compounds able to increase the susceptibility of Gram-negative pathogens to antibiotics, as erythromycin or vancomycin, with poor activity against these microorganisms [32]. Besides increasing the bacterial susceptibility to antimicrobials, these compounds may have also antibiofilm activity, a property of some EPIs (including catechol) extracted from maple syrup [47]. Constituents of essential oils, such as the monoterpene (−)-α-pinene present in Alpinia Katsumadai seeds [48], also inhibit the activity of Gram-negative efflux pumps. Indeed, (−)-α-pinene inhibits the CmeABC and Cj1687 efflux pumps and consequently increases de susceptibility of Campylobater jejuni to ciprofloxacin, erythromycin, and triclosan [48]. Given its clinical relevance, different works have focused on the search of plant-derived inhibitors of P. aeruginosa efflux pumps. Among them, lanatoside C, diadzein, conessine, berberine, and palmatine present in Digitalis lanata, Glycine max, Holarrhena antidysenterica, and Berveris bulgaris, respectively [49–51], inhibit the activity of MexAB, an efflux pump with a relevant role in the intrinsic resistance to antibiotics of P. aeruginosa [36]. Lanatoside C and diadzein also have EPI activity against the E. coli AcrAB efflux pump, indicating that these inhibitors are not fully specific [49]. Other EPIs capable to inhibit the activity of E. coli efflux pumps are ursolic acid from Eucalyptus tereticornis [52], lysergol from Ipomea muricata [53], gallotannin 1,2,6-tri-O-galloyl-β-d-glucopyranose from Terminalia chebula [54], 4-hydroxy-α-tetralone combined with its semisynthetic derivatives from Ammannia spp. [55] and plumbagin, nordihydroguaretic acid, and shikonin from Plumbago indica, Larrea tridentata, and Lithospermum erythrorhizon, respectively [56]. Altogether, these findings indicate that plants can be a good source of EPIs that may belong, among others, to the groups of phenolic and aromatic compounds, flavones, alkaloids, or tannins.
Current medicines hold promise in the treatment of orphan infections due to brain-eating amoebae
Published in Expert Opinion on Orphan Drugs, 2021
Ruqaiyyah Siddiqui, Mohamed Yehia Abouleish, Mustafa Khamis, Taleb Ibrahim, Naveed Ahmed Khan
Among related protozoa, Entamoeba histolytica is a parasitic amoeba and a causative agent of amoebiasis that has remained a significant problem in human health. Intensive drug discovery research has identified a plethora of compounds to target E. histolytica[7]. Given the similarities in the cell biology, virulence traits such as proteases, motility, physiology, cellular differentiation, biochemistry etc., it is reasonable to test anti-E. histolytica compounds against pathogenic amoebae. Using the recently available genome information for brain-eating amoebae, it makes sense to investigate compounds with known parasite-specific target(s). As long as targets are confirmed in the brain-eating amoebae, this approach can be fruitful in identifying potentially novel bioactive molecules. Anti-protozoal compounds with demonstrated activity against E. histolytica are listed below and include synthetic as well as natural products[7]. Among synthetic thiosemicarbazones, two thiophene-2-carboxaldehyde thiosemicarbazones containing 4- benzylpiperidine and adamantamine moieties at N4 position are most active against amoebiasis. 2-Acetylpyridine dithiocarbazates, 1,2,4-triazine showed potent effects against E. histolytica. Among oxime ethers, µ-bis(oxo)bis{oxovanadium(V)} complexes of 2-acetylpyridine hydrazones derived from nicotinic acid & 2-furoic acid hydrazide displayed higher activity than metronidazole. Among bisphosphonates, bisphosphonates containing nitrogen were found bioactive against E. histolytica. Among alkaloids, emetine, isolated from Cephaelis ipecacuanha showed potent activity against Entamoeba. Naturally occurring alkaloid cryptopleurine, usambarensine, matrine, conessine, and benzylisoquinoline alkaloid, berberine exhibited activity. Among bisbenzylisoquinoline alkaloids, aromoline, isotrilobine, and insularine were found active against E. histolytica. Among quassinoids, triterpenes, quassin, glaucarubin showed bioactivity. Among nonalkaloid natural products, anemonin, mangostin, marmelosin, were anti-protozoal. Among iridoids, specioside, verminoside, and minecoside, showed anti-protozoal effects similar to metronidazole. Among flavonoids, luteolin, kaempferol, apigenin, showed potent effects. Among polyphenolic compounds, gossypol showed remarkably greater anti-protozoal effects when compared with metronidazole and worth investigation against pathogenic free-living amoebae.