Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology

Lal, Nand; Jangir, Santosh; Bala, Veenu; Mandalapu, Dhanaraju; Sarswat, Amit; Kumar, Lalit; Jain, Ashish; Kumar, Lokesh; Kushwaha, Bhavana; Pandey, A. K.; Krishna, Shagun; Rawat, Tara; Shukla, Praveen Kumar; Maikhuri, Jagdamba P.; Siddiqi, Mohammad Imran; Gupta, Gopal; Sharma, Vishnu L.

doi:10.1016/j.ejmech.2016.03.012

Cited by 16 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While simple tetraalkylthiuram disulfides, which are oxidized forms of dithiocarbamate anions, are widely supplied and inexpensive, variants such as i Bu 2 NC(S)SSC(S)N i Bu 2 that are less available commercially are nonetheless readily prepared. Procedures describing the synthesis of i Bu 2 NC(S)SSC(S)N i Bu 2 from the reaction between i Bu 2 NH and CS 2 in aqueous base − have, in our hands, been found to be attended by significant competing reaction pathways. This observation motivated our implementing a clean, effective modification that simply employs excess i Bu 2 NH in CS 2 /EtOH (Scheme ).…”

Section: Resultsmentioning

confidence: 80%

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

et al. 2019

View full text Add to dashboard Cite

Irradiation at 460 nm of [Mo 3 (μ 3 -S)(μ 2 -S 2 ) 3 (S 2 CNR 2 ) 3 ]I ([2a]I, R = Me; [2b]I, R = Et; [2c]I, R = i Bu; [2d]I, R = CH 2 C 6 H 5 ) in a mixed aqueous−polar organic medium with [Ru(bipy) 3 ] 2+ as photosensitizer and Et 3 N as electron donor leads to H 2 evolution. Maximum activity (300 turnovers, 3 h) is found with R = i Bu in 1:9 H 2 O:MeCN; diminished activity is attributed to deterioration of [Ru(bipy) 3 ] 2+ . Monitoring of the photolysis mixture by mass spectrometry suggests transformation of [Mo 3 (μ 3 -S)(μ 2 -S 2 ) 3 (S 2 CNR 2 ) 3 ] + to [Mo 3 (μ 3 -S)(μ 2 -S) 3 (S 2 CNR 2 ) 3 ] + via extrusion of sulfur on a time scale of minutes without accumulation of the intermediate [Mo 3 S 6 (S 2 CNR 2 ) 3 ] + or [Mo 3 S 5 (S 2 CNR 2 ) 3 ] + species. Deliberate preparation of [Mo 3 S 4 (S 2 CNEt 2 ) 3 ] + ([3] + ) and treatment with Et 2 NCS 2 1− yields [Mo 3 S 4 (S 2 CNEt 2 ) 4 ] ( 4), where the fourth dithiocarbamate ligand bridges one edge of the Mo 3 triangle. Photolysis of 4 leads to H 2 evolution but at ∼25% the level observed for [Mo 3 S 7 (S 2 CNEt 2 ) 3 ] + . Early time monitoring of the photolyses shows that [Mo 3 S 4 (S 2 CNEt 2 ) 4 ] evolves H 2 immediately and at constant rate, while [Mo 3 S 7 (S 2 CNEt 2 ) 3 ] + shows a distinctive incubation prior to a more rapid H 2 evolution rate. This observation implies the operation of catalysts of different identity in the two cases.

show abstract

Section: Resultsmentioning

confidence: 80%

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, several hits are potentially of interest. One is Disulfiram (70% maximum reduction at 10 μM), a drug that is well tolerated, has long been used for treating alcohol dependency and has previously been shown to inhibit sperm motility (Lal et al , 2016). Disulfiram is unlikely to be developable as a suitable contraceptive drug due to its side-effects when alcohol is consumed but has potential to facilitate mode-of-action studies.…”

Section: Discussionmentioning

confidence: 99%

A phenotypic screening platform utilising human spermatozoa identifies new compounds with contraceptive activity

Barratt

Andrews

Gruber

2019

Preprint

View full text Add to dashboard Cite

24There is an urgent need to develop new methods for male contraception, however a major barrier to drug discovery 25 has been the lack of validated targets and the absence of an effective high-throughput phenotypic screening system. To 26 address this deficit, we developed a fully-automated robotic screening platform that provided quantitative evaluation 27 of compound activity against two key attributes of human sperm function: motility and acrosome reaction. In order to 28 accelerate contraceptive development, we screened the comprehensive collection of 12,000 molecules that make up 29 the ReFRAME repurposing library, comprising nearly all the small molecules that have been approved or have undergone 30 clinical development, or have significant preclinical profiling. We identified several compounds that potently inhibit 31 motility representing either novel drug candidates or routes to target identification. This platform will now allow for 32 major drug discovery programmes that address the critical gap in the contraceptive portfolio as well as uncover novel 33 human sperm biology. 34 35 36 Introduction. 38An effective and comprehensive family planning strategy is fundamental to delivery on the United Nations 17 39 Sustainable Development Goals (Starbird et al., 2016; Goodkind et al., 2018), however the current contraceptive 40 portfolio is suboptimal. For example, it is estimated that more than 214 million women in developing countries have an 41 unmet need for contraception which results in 89 million unintended pregnancies and 48 million abortions every year, 42 with substantial impacts on maternal and child health and poverty levels (Guttmacher Institute, 2017). To achieve the 43 UN targets it is critical that involvement of men be considered of equal importance as women (Hardee et al., 2016). 44However, it is noticeable that no effective, reversible and widely-available form of contraception has been developed 45 for men since the condom and as such the burden falls largely on the woman. The development of drugs that can be 46 used in the male would address a critical gap in the contraceptive portfolio. 48Progress in developing new male contraceptives has been slow for a plethora of reasons. Despite decades of research, 49 safe and effective hormonal approaches have yet to be realised and viable alternatives remain elusive (Page and Amory, 50 2018). Developing a drug for any purpose is difficult but one that blocks sperm function is a particular challenge as 72 chemical diversity libraries for novel medicinal chemistry start points. 74 Results 75Phenotypic Assay Development 76Our automated platform ( Figure 1A) allows for the identification of relatively fast-acting compounds with a rapid plate-77 processing time (~75 minutes/ 384-well plate), where the motility assay runs for ~30 minutes followed directly by the 78 AR assay (~ 45 minutes). Automated cell tracking (Figure 1B & Supplementary Figure 1A) using time-lapse images 100 the AR hits were found to be true positives (see examples in Supplementary F...

show abstract

“…A); (ii) the reaction of alkyl halides and tetramethylthiuram disulfides, which are commonly prepared by the oxidative coupling of dialkylcarbamodithioic acid salts (Scheme , eq. B); (iii) the reaction of amines with expensive and toxic reagents, such as thiophosgene or isothiocyanate; and (iv) ring‐opening reactions of epoxides and N ‐tosyl aziridines with dialkylcarbamodithioic acid salts (Scheme , eq. C).…”

Section: Methodsmentioning

confidence: 99%

Copper‐Catalyzed C−S Coupling of Quaternary Ammonium Salts and Dialkylcarbamodithioic Acid Salts

et al. 2020

View full text Add to dashboard Cite

An efficient synthesis of (chiral) alkyl dialkylcarbamodithioates via a CuI-catalyzed CÀ S cross-coupling reaction of (chiral) quaternary ammonium salts and (chiral) dialkylcarbamodithioic acid salts has been developed. CÀ S coupling products were obtained with extremely high ee values and yields, with enantioenriched arylmethyl trimethylammonium triflates affording the inverse absolute configuration.

show abstract

Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology

Cited by 16 publications

References 41 publications

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

A phenotypic screening platform utilising human spermatozoa identifies new compounds with contraceptive activity

Copper‐Catalyzed C−S Coupling of Quaternary Ammonium Salts and Dialkylcarbamodithioic Acid Salts

Contact Info

Product

Resources

About

Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology

Cited by 16 publications

References 41 publications

Photocatalytic H2-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

Photocatalytic H2-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

A phenotypic screening platform utilising human spermatozoa identifies new compounds with contraceptive activity

Copper‐Catalyzed C−S Coupling of Quaternary Ammonium Salts and Dialkylcarbamodithioic Acid Salts

Contact Info

Product

Resources

About

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands

Photocatalytic H₂-Evolution by Homogeneous Molybdenum Sulfide Clusters Supported by Dithiocarbamate Ligands