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Anti-proliferative activity, molecular modeling studies and interaction with calf thymus DNA of novel ciprofloxacin analogues

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Abstract

In our pursuit to expand new potential anticancer leads, a series of eighteen novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized and evaluated anti-proliferative activity against five human cancer cell lines such as A549 (lung cancer), Mia Paca (pancreatic cancer), HeLa (cervical cancer), MDA MB-231 (breast cancer), MCF-7 (breast cancer) and normal embryonic kidney cell line (HEK) were carried out using MTT assay. Few of the synthesized analogues exhibited potent anticancer activity against the cancer cell lines at a lower concentration. The synthesized compounds showed the less toxic effect on normal human embryonic kidney cell line (HEK) compared with doxorubicin. Noticeably, compound 3o exhibited potent activity against all five cancer cell lines compared with ciprofloxacin. Further study exposed that compound 3o could competently intercalate into calf thymus DNA to form 3o-DNA complex which might block DNA replication to apply anti-proliferative activity. Docking simulation studies supported by molecular interactions with DNA type II topoisomerase. These derivates can become lead structures for the development of potential anticancer drugs.

Graphical Abstract

Eighteen CP analogues were synthesized and evaluated for anti-proliferative activity. The interactions with DNA topoisomerase II were supported by molecular docking studies. 3o showed promising anticancer activity than CP against MCF7 cell line and interaction with calf thymus DNA was studied by fluorescence spectroscopy.

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Acknowledgements

Sincere thanks to the Department of Biotechnology (No.BT/PR4801/MED/29/370/2012), Government of India, New Delhi for funding the project. The author NS thanks UGC, New Delhi for the award of senior research fellowship; we also thank Devendar for maintaining cell culture.

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Authors and Affiliations

  1. Department of Chemistry, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, Telangana, 500 078, India

    Narva Suresh, Amaroju Suresh & Kondapalli Venkata Gowri Chandra Sekhar

  2. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Telangana, 500 076, India

    Suresh Yerramsetty & Manika Pal Bhadra

  3. National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, Telangana, 500 037, India

    Mallika Alvala

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  1. Narva Suresh
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  2. Amaroju Suresh
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  3. Suresh Yerramsetty
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  4. Manika Pal Bhadra
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  5. Mallika Alvala
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Correspondence to Kondapalli Venkata Gowri Chandra Sekhar.

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Suresh, N., Suresh, A., Yerramsetty, S. et al. Anti-proliferative activity, molecular modeling studies and interaction with calf thymus DNA of novel ciprofloxacin analogues. J Chem Sci 130, 121 (2018). https://doi.org/10.1007/s12039-018-1528-y

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  • DOI: https://doi.org/10.1007/s12039-018-1528-y

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