eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-10-10 23 3 59978 article Shantanu Sanjay Ghodke 1 Dinesh Dattatray Rishipathak 1 Department of Pharmaceutical Chemistry, MET’s Institute of Pharmacy, Savitribai Phule Pune University, Nashik, India Benzothiophene (benzo[b]thiophene, C₈H₆S) is a privileged sulfur-containing heterocyclic scaffold in drug discovery, combining a rigid, near-planar aromatic framework (calculated Log P ≈ 2.78, molecular weight ≈ 134.20 g/mol) with the clinical precedent of approved agents such as raloxifene, zileuton, and sertaconazole. Although individual synthetic and biological studies on benzothiophene continue to accumulate rapidly, no recent review has jointly integrated post-2020 green and metal-free synthetic advances with the emerging biological literature on multidrug-resistant pathogens and multi-target kinase inhibition, while also critically separating experimentally demonstrated activity from in silico predictions. this review synthesises synthetic methodologies (2007–2024, with emphasis on post-2020 reports) alongside biological data on antimicrobial, anticancer, central nervous system, anti-inflammatory, antioxidant, and antidiabetic activity, and evaluates the structure–activity relationships (SAR) and mechanistic evidence reported for each area. Recent metal-free, aqueous, and photochemical cyclisation strategies provide complementary routes to substituted benzothiophenes, while selected derivatives show sub-micromolar in vitro potency against multidrug-resistant Staphylococcus aureus, colistin-resistant Gram-negative pathogens, and kinase targets including DYRK1A/B, VEGFR-2, EGFR, and PLK1-PBD; however, this evidence is derived overwhelmingly from in vitro and in silico studies, with in vivo pharmacokinetic and toxicological data remaining limited for most compound classes. Benzothiophene remains a versatile and pharmacologically tractable scaffold but realising its translational potential will require systematic pharmacokinetic profiling, resistance-mechanism studies, and green-chemistry metrics that are largely absent from the current primary literature. https://www.biotech-asia.org/vol23no3/benzothiophene-derivatives-as-multi-target-kinase-inhibitors-and-antimicrobial-agents-against-multidrug-resistant-pathogens-advances-in-green-and-metal-free-synthetic-methodologies/ Benzo[b]thiophene; green and metal-free synthesis; multidrug-resistant pathogens; multi-target kinase inhibitors; structure–activity relationship; in silico drug design