title: Design and synthesis of γ-butyrolactone derivatives as potential spermicidal agents.
abstract: A series of γ-butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartrate salts and were evaluated for spermicidal activity against human sperm in vitro. Compounds showing appreciable spermicidal activity at ⩽0.5% [3c, 4d (0.5%); 2c, 3d (0.1%); 2d, 4c (0.05%)] were tested for safety studies against human cervical (HeLa) cell line. These compounds were found safer than, Nonoxynol-9. One of the two most active compounds was also found to be the safest (IC50=961 μg/ml; 4c), while the second compound exhibited lower safety against HeLa (IC50=269 μg/ml; 2d). The compound 4c significantly reduced the number of free thiols on human sperm. All the compounds were inactive against Trichomonas vaginalis.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Rishi Ranjan
authors.initials: RR
authors.lastname: Pandey
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Akansha
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Shakti Deep
authors.initials: SD
authors.lastname: Pachauri
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Khandelwal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Arshi
authors.initials: A
authors.lastname: Naqvi
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Malasoni
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Kushwaha
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kumar
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Jagdamba Prasad
authors.initials: JP
authors.lastname: Maikhuri
authors.affiliation: Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Pandey
authors.affiliation: Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Paliwal
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: anilcdri@gmail.com.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D015107:4-Butyrolactone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D008297:Male; D015394:Molecular Structure; D013089:Spermatocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013094:Spermatozoa / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000037:antagonists & inhibitors; D014246:Trichomonas vaginalis / Q000187:drug effects
chemical_list: D013089:Spermatocidal Agents; D013438:Sulfhydryl Compounds; D015107:4-Butyrolactone
keywords: Butyrolactone derivatives; HeLa cells; Spermicides; Thiols