title: Immunomodulatory Response Triggered by the Alkaloids, 3-Amino-7-Benzylbenzimidazo[3,2-a] Quinolinium Chloride (ABQ-48) and 3-Nitro-7-Benzylbenzimidazo [3,2-a] Quinolinium Chloride (NBQ-48).
abstract: ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-a]quinolinium chloride) and NBQ-48 (3-nitro-7-benzylbenzimidaw[3,2-a] quinolinium chloride) are un-natural alkaloids containing a planar heteroaromatic systems characterized by quaternized nitrogen fused to benzothiazole nucleus. Both compounds are structurally related to naturally occurring substances such as elliptine (from Ochrosia), and berberine (from Berberis). Previous in vitro studies have shown these agents to control tumor-cell proliferation indicating that both BQS are active but especially ABQ-48 at a 1 OuM dose with over 80% control of the proliferation of multiple cancer cell lines from various etiologies including colon, melanoma, CNS and ovarian cells. Mechanism of action studies have also been conducted however this is the first approach to evaluate immune modulatory activity of these novel BQS. Immune-based therapy is an increasing field in which scientists identify how the immunomodulatory activity of known and newly discovered compounds elicits an immune response that could be used against diseases. In this study, our main objective was to apply an in vitro model to show the immunomodulatory effects of ABQ-48 and NBQ-48 by analyzing the cytokine profile resulting after extracted murine spleen cells were treated with both BQS using a fluorescence-based multiplex ELISA approach. Screened cytokines included: G-CSF, GM-CSF, IL-1a, IL-2, IL-3, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-21, IL-23, IFN-γ, and TNF-α. Our study results show ABQ 48 and NBQ-48 to stimulate the release of G-CSF, IL-2, IL-6, and, IFN-γ when mouse splenocytes are incubated with serial dilutions of these agents. Our finding opens new possibilities of potentially using ABQ-48 and NBQ-48 as immunomodulatory agents; with intend to activate the immune system such as the production of neutrophils against cancer or reducing chemotherapy side effects.
authors.affiliation: Department of Microbiology and Medical Zoology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.affiliation: Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Zayas
authors.affiliation: Department of Microbiology and Medical Zoology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico ; Universidad Central del Caribe, School of Medicine, Department of Microbiology and Immunology, Bayamon, Puerto Rico.
authors.forename: Eric
authors.initials: E
authors.lastname: Miranda
authors.affiliation: Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: Christian
authors.initials: C
authors.lastname: Velez
authors.affiliation: Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: Wigberto J
authors.initials: WJ
authors.lastname: Hernandez
authors.affiliation: Department of Chemistry, University of Puerto Rico at Mayaguez, Mayaguez, Puerto Rico.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Rivera
authors.affiliation: Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Cox
keywords: Alkaloids; Anti cancer; BQS; Hypoxia; Immune modulation