{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:53:22Z","timestamp":1782698002051,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T00:00:00Z","timestamp":1534723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leprosy (causative, <jats:italic>Mycobacterium leprae<\/jats:italic>) continues to be the persisting public health problem with stable incidence rates, owing to the emergence of dapsone resistance that being the principal drug in the ongoing multidrug therapy. Hence, to overcome the drug resistance, structural modification through medicinal chemistry was used to design newer dapsone derivative(s) (DDs), against folic acid biosynthesis pathway. The approach included theoretical modeling, molecular docking, and molecular dynamic (MD) simulation as well as binding free energy estimation for validation of newly designed seven\u00a0DDs, before synthesis. Theoretical modeling, docking, and MD simulation studies were used to understand the mode of binding and efficacy of DDs against the wild\u2010type and mutant dihydropteroate synthases (DHPS). Principal component analysis was performed to understand the conformational dynamics of DHPS\u2010DD complexes. Furthermore, the overall stability and negative\u2010binding free energy of DHPS\u2010DD complexes were deciphered using Molecular Mechanics\/Poisson\u2010Boltzmann Surface Area technique. Molecular mechanics study revealed that DD3 possesses higher binding free energy than dapsone against mutant DHPS. Energetic contribution analysis portrayed that van der Waals and electrostatic energy contributes profoundly to the overall negative free energy, whereas polar solvation energy opposes the binding. Finally, DD3 was synthesized and characterized using Fourier\u2010transform infrared spectroscopy, UV, liquid chromatography\u2010mass spectrometry, and proton nuclear magnetic resonance techniques. This study suggested that DD3 could be further promoted as newer antileprosy agent. The principles of medicinal chemistry and bioinformatics tools help to locate effective therapeutics to minimize resources and time in current drug development modules.<\/jats:p>","DOI":"10.1002\/jcb.27304","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T15:04:50Z","timestamp":1534777490000},"page":"9838-9852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Molecular docking and simulation study for synthesis of alternative dapsone derivative as a newer antileprosy drug in multidrug therapy"],"prefix":"10.1002","volume":"119","author":[{"given":"Shasank S.","family":"Swain","sequence":"first","affiliation":[{"name":"Central Research Laboratory, Institute of Medical Sciences and Sum Hospital, Siksha \u201cO\u201d Anusandhan (Deemed to be University)  Bhubaneswar Odisha India"},{"name":"NCDs Division ICMR\u2010Regional Medical Research Centre  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir K.","family":"Paidesetty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmaceutical Sciences, Siksha \u201cO\u201d Anusandhan (Deemed to be University)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Budheswar","family":"Dehury","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Centre, ICMR\u2010Regional Medical Research Centre  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotirmaya","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmaceutical Sciences, Siksha \u201cO\u201d Anusandhan (Deemed to be University)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundeep Chaitanya","family":"Vedithi","sequence":"additional","affiliation":[{"name":"Schieffelin Institute of Health\u2010Research and Leprosy Centre (SIH R &amp; LC), Karigiri  Vellore Tamil Nadu India"},{"name":"Department of Biochemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7695-831X","authenticated-orcid":false,"given":"Namita","family":"Mahapatra","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Centre, ICMR\u2010Regional Medical Research Centre  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahziba","family":"Hussain","sequence":"additional","affiliation":[{"name":"NCDs Division ICMR\u2010Regional Medical Research Centre  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabindra N.","family":"Padhy","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Institute 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