Pyrazoline B-Paclitaxel or Doxorubicin Combination Drugs Show Synergistic Activity Against Cancer Cells: In silico Study.

Wiraswati, Hesti Lina; Bashari, Muhammad Hasan; Alfarafisa, Nayla Majeda; Ma'ruf, Ilma Fauziah; Sholikhah, Eti Nurwening; Wahyuningsih, Tutik Dwi; Satriyo, Pamungkas Bagus; Mustofa, Mustofa; Satria, Denny; Damayanti, Ema

Background: Multidrug resistance in various cancer types is a major obstacle in cancer treatment. The concept of a single drug molecular target often causes treatment failure due to the complexity of the cellular processes. Therefore, combination chemotherapy, in which two or more anticancer drugs are co-administered, can overcome this problem because it potentially have synergistic efficacy besides reducing resistance, and drug doses. Previously, we reported that pyrazoline B had promising anticancer activity in both in silico and in vitro studies. To increase the efficacy of this drug, co-administration with established anticancer drugs such as doxorubicin and paclitaxel is necessary. Materials and Methods: In this study, we used an in silico approach to predict the synergistic effect of pyrazoline B with paclitaxel or doxorubicin using various computational frameworks and compared the results with those of an established study on the combination of doxorubicin-cyclophosphamide and paclitaxel-ascorbic acid. Results and Discussion: Drug interaction analysis showed the combination was safe with no contraindications or side effects. Furthermore, molecular docking studies revealed that doxorubicin-pyrazoline B and doxorubicin-cyclophosphamide may synergistically inhibit cancer cell proliferation by inhibiting the binding of topoisomerase I to the DNA chain. Moreover, the combination of pyrazoline B-paclitaxel may has synergistic activity to cause apoptosis by inhibiting Bcl2 binding to the Bax fragment or inhibiting cell division by inhibiting α-β tubulin disintegration. Paclitaxel-ascorbic acid had a synergistic effect on the inhibition of α-β tubulin disintegration. Conclusion: The results show that this combination is promising for further in vitro and in vivo studies.

DNA topoisomerase I; PACLITAXEL; INHIBITION of cellular proliferation; CANCER cells; DOXORUBICIN; CANCER cell proliferation; ANTINEOPLASTIC agents; CELL division

Advances & Applications in Bioinformatics & Chemistry, 2024, Vol 17, p33

1178-6949

Academic Journal

10.2147/AABC.S452281