Upendra Chaudhary^1,, Vijay Gurung², Sayed Tariq Pachakhan², Jhashanath Adhikari Subin³, Yuba Raj Pokharel^2,* and Paras Nath Yadav^1,*

¹Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal

²Faculty of Life Science and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi-110021, India

³Department of Chemistry, D.A.V. College, Jawalakhel, Lalitpur 44700, Nepal

*Corresponding authors: E-mail: yrp@sau.ac.in; pnyadav219@gmail.com

(Z)-N-ethyl-2-(5-methoxy-2-oxoindolin-3-ylidene)hydrazine-1-carbothioamide (MeOIstEt) and (Z)-2-(5-methoxy-2-oxoindolin-3-ylidene)-N-methylhydrazine-1-carbothioamide (MeOIstMe) were synthesized and subjected to elemental analysis and various characterization techniques viz. IR, ¹H NMR, ¹³C NMR, UV-Vis and HRMS. The synthesized N(4)-alkyl substituted thiosemicarbazones were evaluated for their anticancer activity against various cancer cell lines like breast cancer (MCF-7), skin cancer (A431) and lung cancer (A549). In micromolar concentrations, the synthesized compounds exhibited moderate anticancer activity (IC₅₀, 6.59-36.49 μM). The compound MeOIstEt was found to be more effective than MeOIstMe against A549 and MCF-7 cell lines, whereas compound MeOIstMe was found to be more potent against A431 cell lines. From flexible receptor molecular docking calculations in a hydrated environment, one of the compounds showed better binding affinity than one FDA approved drug. The insights from computational studies have strengthened the experimental findings and vice-versa. This work demonstrates the role of multiple approaches in finding better drug candidate with efficient anti-cancer properties.

Anticancer activity, Breast cancer, 5-Methoxyisatin, Molecular docking, Thiosemicarbazones.