Abstract
Abstract Derivatives of podophyllotoxin, namely etoposide (2), etopophos (3) and teniposide (4) have been developed and are currently used in clinic for the treatment of a variety of malignancies. Due to structural complexity of podophyllotoxin, commercial synthesis, further derivative synthesis and structural modifications of podophyllotoxin are limited. We have developed some heterocyclic analogues of podophyllotoxin i.e. N-hydroxyethyl-4-aza-podophyllotoxin derivatives (AZPs). Advantage of these compounds is their easy and fast synthesis as compared to the parent natural lignin i.e. podophyllotoxin. Owing to their promising activity against 60 cell lines at NCI, we further expanded the library of AZPs substituted at ring A and E. This was followed by a screen of in vivo activity using a panel of tumor hollow-grafts implanted in mice consisting of breast (MDA-MB-231), non-small lung (NCI-H23 and NCI-H522), colon (SW-620 and COLO 205), melanoma (UACC-62, MDA-MB-435 and LOXIMVI), ovarian (OVCAR-5 and OVCAR-3) and CNS (U251 and SF-295) cell lines. These new compounds shows comparatively excellent activity against several human cancer cell lines at NCI. We recently reported activity of AZPs in MTA resistant Cancer Cells. We are now reporting immunomodulatory effect of our AZPs for the first time, assessed by in-vitro stimulation of mouse lymphocytes for five days. Specifically, our preliminary data shows AP-102, AP-103, AP-104, and AP-205 to induce 2208, 2575, 2071, and 7166 pg/mL of G-CSF, respectively, and the AP-311, AP-312, AP-102, AP-103, AP-104, and AP-205 induced 551, 810, 772, 1125, 782, and 4351 pg/mL of IL-6, respectively. These data demonstrate the immunostimulatory ability of our AP compounds. Further experiments need to be performed to study the impact of these compounds in the modulation of the immune system. Citation Format: Ajay Kumar, Eric Miranda Valentin, Miguel Otero. Immunomodulatory activity of aza-podophyllotoxin derivatives. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4285. doi:10.1158/1538-7445.AM2015-4285
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
