INDOLE BASED ALKALOID IN CANCER: AN OVERVIEW
Ramit Singla1, Arvind Negi1*, Virendra Singh2
1Centre for Chemical and pharmaceutical sciences, Central university of Punjab, Bathinda, India
2Department of Chemistry, National institute of technology, Jalandhar, India
Indole alkaloids are well characterized for diverse activities. Meanwhile, the present scenarioof disease depicting a different story, urge a call for novel scaffolds and pharmacophores. In recent years, indole based alkaloids gain significant importance in cancer chemotherapy and used as an adjuvant especiallyin case of Vinca alkaloids. These reports encourage the researchers for new finding related to indole based alkaloids to retrieve better scaffold for designing and synthesis of anticancer agents. However we tried to compile the literature which cover the recent reports and updates of indole based alkaloids targeting incancer. Moreover this review paperbrings new dimension and interface between the indole based alkaloids and their valuable commitment towards cancer targeting.
REFERENCE ID: PHARMATUTOR-ART-2089
PharmaTutor (ISSN: 2347 - 7881)
Volume 2, Issue 1
Received On: 01/012/2014; Accepted On: 22/12/2014; Published On: 15/01/2014
How to cite this article: A Negi, R Singla, V Singh, Indole Based Alkaloid in Cancer: An Overview, PharmaTutor, 2014, 2(1), 76-82
Cancer cells are quite similar to the normal cells, expect the advancement in the signalling which makes them immortal. They readily adapt to starvation microenvironments, and modify their protein-nucleic acid machinery to assure their continued survival so that theycan able to utilize the altered mechanisms to promote cellular immortality. All these hallmarksof cancer makechallenging task to target the cancerous cells.
Moreover modern cancer chemotherapy utilizes following strategies to target the cancer as follows:
· Combined modality chemotherapywhich uses the drugs together with radiation therapy or surgery.
· Neoadjuvant chemotherapy(preoperative treatment)
· Adjuvant chemotherapy(postoperative treatment) is used where there is a risk of recurrence after the surgery.
· Palliative chemotherapyis implicated to increase the life expectancy.
These chemotherapeutic drugs can be majorly classified as:
Natural products, especially those ones which are extracted\obtained from plant origin, have been used for the treatment of various diseases since ancient times and can be witnessed in the numerous ancient\traditional medicinal plant books. In present circumstances where disease modulated themselves to a new level of adaptation (resistance) and modifies.Therefore new scaffolds or pharmacophore are much needed to overcome these issues. Moreover cancer is one such disease and therefore alternatively plant derived agents are being employed for the treatment of cancer. Several natural derived anticancer agents including Taxol, Vinblastine, Vincristine, Camptothecin derivatives, Topotecan and Irinotecan, and Etoposide are in clinical use. Even a number of promising agents such as flavopiridol, roscovitine, combretastatin A-4, betulinic acid and silvestrol are in clinical or preclinical development.
The Indole alkaloids are the major classof alkaloids which turn outinto different anti-cancerous scaffolds, enlisted as:
Vinblastine and vincristine
Indole is a basic heterocyclic scaffold which was originatedwith the study of a dye, indigo.Thisscaffold is composed of abenzopyrrole, in which the benzene and pyrrole rings are fusedviaC2 and C3 positions of the pyrrolenucleus(see in Fig.1.).Its presence in the nature is highly versatile even it isfound endogenously in human e.g. tryptophan amino acid. Moreover natural secondary metabolite (alkaloids)contain indole nucleus which is ubiquitously present in nature including plantslike (vincristine), marine creatures (manzamines), insects, fungal metabolites (cytochalasins), mammalian as well as human tissues, and body fluids.
Fig. 1. Structure of indole.
This review covers some of the active indole derivatives which have shown anticancer activity. These includes Non-isoprenoidtryptamine, Piperazinedione, Indoloiminoquinolines, β-Carbolines,Bisindole, Cytochalasins, Elliptinium, Vinblastine and Vincristine.
Fig.2. Depicting the different alkaloids possessing the anticancer activity.
Indole-based natural products as Anticancer Agents
Two new bioactive indole alkaloids, Bufobutanoic acid (2) and Bufopyramide (3) wereisolated from the skin secretions of the local toads Bufobufogarigarizans or Bufomelanostrictus. Both compounds exhibited cytotoxicity against murine P388 lymphocytic leukemia cells with IC50 values of 22 µg mL-1 and 26 µg mL-1, respectively[1-4]see in fig.3.
Fig. 3.Structure of anti-cancerous Non-isoprenoid tryptamines.
Two cytotoxic epidithiodioxopiperadine dimers, 11,11’-dideoxyverticillin A (4) and 11’ deoxyverticillin A (5) together with known Verticillin A, had been isolated from the mycelium of a marine-derived fungus of the genusPenicillium. Cytotoxicity against HCT-116 human colon carcinoma of compounds (4) and (5) have been described (IC50 = 30 ngML-1)see in fig.4.
Fig. 4.Structure of piperazinedionesalkaloids
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