Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Leishmaniasis control profoundly depends upon chemotherapy which includes pentavalent antimonials, paromomycin, pentamidine, amphotericin B and miltefosine. Miltefosine is the only oral drug used for the treatment of Visceral Leishmaniasis with high cure rate but decrease in susceptibility is observed in countries like India where it is extensively used. Hence, there is an urgent need to develop novel antileishmanial agents with good potency and better therapeutic profile. Manzamines are unique group of β-carboline alkaloids isolated from marine sponges and exhibited potent antileishmanial activity. In the present study, we described antileishmanial activity, cytotoxicity and structure activity relationship of natural manzamine alkaloids.
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http://dx.doi.org/10.1016/j.ejmech.2014.07.006 | DOI Listing |
Eur J Pharmacol
January 2025
Department of Urology, Brown Cancer Center, 505 S Hancock Street, Louisville, KY, USA. Electronic address:
Manzamine A, a natural compound derived from various sponge genera, features a β-carboline structure and exhibits a range of biological activities, including anti-inflammatory and antimalarial effects. Its potential as an anticancer agent has been explored in several tumor models, both in vitro and in vivo, showing effects through mechanisms such as cytotoxicity, regulation of the cell cycle, inhibition of cell migration, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis through multi-target interactions of E2F transcriptional factors, ribosomal S6 kinases, androgen receptor (AR), SIX1, GSK-3β, V-ATPase, and p53/p21/p27 cascades. This systematic review evaluates existing literature on the potential application of this marine alkaloid as a novel cancer therapy, highlighting its promising ability to inhibit cancer cell growth while causing minimal side effects.
View Article and Find Full Text PDFMol Divers
May 2024
Department of Pharmaceutical Chemistry and Quality Assurance, L. M. College of Pharmacy, Navrangpura, Ahmedabad, 380 009, Gujarat, India.
Malaria caused by P. falciparum, has been recognized as one of the major infectious diseases causing the death of several patients as per the reports from the World Health Organization. In search of effective therapeutic agents against malaria, several research groups have started working on the design and development of novel heterocycles as anti-malarial agents.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
August 2024
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.
View Article and Find Full Text PDFMol Oncol
August 2024
Department of Drug Discovery and Biomedical Sciences and Public Health, Colleges of Pharmacy and Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs.
View Article and Find Full Text PDFOrg Lett
March 2024
Université Paris-Saclay, CNRS, BioCIS, Chimie des Substances Naturelles, 91400 Orsay, France.
Inspired by the multicomponent reaction-type scenario involving fatty dialdehydes, a nitrogen source, and acrolein, as a key C unit, put forward by Baldwin and Whitehead to explain the formation of manzamine-type alkaloids, 96 multicomponent reactions were designed, and their analytical readouts were deconvoluted using a herein-provided chemoinformatic workflow. This strategy pinpointed relevant conditions tuning the reactivity of acrolein to fulfill Baldwin and Whitehead's manzamine alkaloids biosynthetic hypothesis. This strategy can become part of a general method for the high-content analysis of multicomponent reactions applied to a natural product biosynthetic scenario.
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