br Acknowledgments This research was supported by a
Acknowledgments This research was supported by a grant from the Korea Health Technology R&D Project through the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C0616). Dr. Jun-Mo Yang was supported by the National R&D Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2017R1D1A1B03029114). Dr. Yong-Doo Park was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP; Ministry of Science, ICT & Future Planning) (No. 2017R1A6A3A11033277).
Introduction α-Glucosidase (EC 126.96.36.199) as a catabolic enzyme hydrolyzes carbohydrates to produce energy, metabolic sugars which are essential for normal physiological functions . In humans, α-glucosidase regulates the body’s plasma glucose levels, providing energy sources to maintain healthy functioning. In contrast, glucose snx synthesis in patients with type-2 diabetes can cause clinically serious problems because high activity of this enzyme increases plasma mellitus glucose levels. Numerous reports address the relevance of α-glucosidase inhibition and the regulation of glucose levels in type-2diabetes mellitus by α-glucosidase inhibitors , , , . Several types of α-glucosidase inhibitors have been clinically applied to inhibit α-glucosidase for medicinal purposes, including acarbose, voglibose and miglitol , , . Inhibitors of this enzyme are designed to be orally taken, acting as an anti-diabetic drug by preventing the digestion of carbohydrates and by delaying the absorption of sugar. This allows plasma glucose to be maintained at a steady level. In addition, α-glucosidase has been proposed as an epididymal marker , possibly contributing to tumor metastasis and growth , , therefore, the study of α-glucosidase has a broad reach that includes inhibitor analysis and development. Bis-indolylmethanes (BIMs) and their derivatives are found in terrestrial and marine metabolites  and they are known to possess a wide range of biological and pharmacological activities such as antimicrobial , antifungal , antibacterial , HIV-1 integrase inhibitor  and aromatase inhibitor for breast cancer . Some of the bis-indolylmethane derivatives are used as estrogen metabolism in humans , in the treatment of fibromyalgia, chronic fatigue and irritable bowel syndrome . Sulfone acts as valuable intermediates in organic synthesis  such as Julia olefination, Ramberg Backlund rearrangement etc. It is also used for construction of building blocks for biologically active compounds. The Sulfone is a diverse structural class associated with antifungal, antibacterial, antitumor agents  and for several enzyme act as inhibitor such as HIV-1 reverse transcriptase , cyclooxygenase-2 (COX-2) , ATPase  and integrin VLA-4 . Our research group has reported the α-glucosidase inhibitory activity of tris-indole hybrid scaffold with oxadiazole ring , α-glucosidase inhibitory and antiglycation activities of oxindole derivatives , , as well as also reported the bis-indolylmethane as potential class of β-glucuronidase inhibitors  (Fig. 1). In continuation of our previous study, we decided to synthesize bis-indolylmethane sulfonohydrazides derivatives 1-14 and evaluation for their α-glucosidase inhibition studies.
Results and discussion
Conclusion With the aim to synthesize more potent α-glucosidase inhibiting agents, new bis-indolylmethane sulfonohydrazides were synthesized through a multistep route. In vitro α-glucosidase inhibition activity of these molecules helped in introducing some new α-glucosidase inhibitors. These derivatives have displayed excellent efficacy against the studied enzyme as compared to standard drug acarbose. All compounds were tested for cytotoxicity and it was found that none of them toxic. The most probable binding modes of these derivatives with enzyme’s active sites were described through molecular docking studies.