**Synthesis, Anticancer Activity, and Molecular Modeling of New Halogenated Spiro[pyrrolidine-thiazolo-oxindoles] Derivatives**

**Mohammad Shahidul Islam 1, Abdullah Mohammed Al-Majid 1, Fardous F. El-Senduny 2, Farid A. Badria 3, A. F. M. Motiur Rahman 4, Assem Barakat 1,5,\* and Yaseen A. M. M. Elshaier 6,\***


Received: 26 February 2020; Accepted: 12 March 2020; Published: 23 March 2020

**Abstract:** A one-pot, single-step, and an atom-economical process towards the synthesis of highly functionalized spirooxindoles analogues was e fficiently conducted to produce a satisfactory chemical yields (70–93%) with excellent relative diastereo-, and regio-selectivity. An in vitro antiproliferative assay was carried out on di fferent cancer cell lines to evaluate the biological activity of the synthesized tetrahydro-1' *<sup>H</sup>*-spiro[indoline-3,5'-pyrrolo[1,2-*c*]thiazol]-2-one **5a–n.** The prepared hybrids were then tested *in vitro* for their antiproliferative e ffects against three cancer cell lines, namely, HepG2 (liver cancer), MCF-7 (breast cancer), and HCT-116 (colon cancer). The spirooxindole analogue **5g** exhibited a broad activity against HepG2, MCF-7, and HCT-116 cell lines of liver, breast, and colorectal cancers when compared to *cis*platin. Modeling studies including shape similarity, lipophilicity scores, and physicochemical parameters were calculated. The results of this study indicated that spirooxindole analogue **5g** retained a good physiochemical parameters with acceptable lipophilicity scores.

**Keywords:** spirooxindole; 1,3-dipolar cycloaddition; eco-friendly chemistry; ROCS; shape alignment; lipophilicity; anticancer activity
