Fertility control is a burning problem all over the world to regulate population overflow and maintain ecological balance. This study is an in-silico approach to explore a non-steroidal lead as contraceptive agent in order to avoid several contraindications generated by steroidal analogues. Piperolactam A, an aristolactam isolated from Piper betle Linn. showed binding affinity towards estrogen and progesterone receptor as -8.9 and -9.0Kcal/mol (inhibition constant Ki=0.294muM and 0.249muM) respectively which is even larger than that of reported antagonists such as Rohitukine and OrgC (binding affinity -8.7 and -8.4Kcal/mol; Ki 0.443muM and 0.685muM respectively). The binding site exploration displayed more hydrogen bonding of Piperolactam A (His 524, Leu 346, Thr 347) than Rohitukine and OrgC (Leu 718) with associated receptors which was further confirmed by molecular dynamics simulations. The drug-likeliness of the compound has been proved from its tally with Lipinsky's Rule of Five and lowered toxicity such as cardiac toxicity, liver toxicity, mutagenicity and ecological toxicity. Endocrine disruptome and later docking guided molecular simulations revealed that Piperolactam A has weaker binding affinity and/or lower probability of binding with nuclear receptors especially hERG and cytochrome P450. The high Caco-2 permeability suggested more bioavailability hence more therapeutic efficacy of the drug.

中文翻译：

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来自蒺藜的胡椒内酰胺 A 作为非甾体抗生育药物开发的新先导药物的药物信息学研究。

生育控制是世界范围内调节人口溢出和维持生态平衡的一个紧迫问题。这项研究是一种在计算机上探索非甾体铅作为避孕药的方法，以避免甾体类似物产生的几个禁忌症。Piperolactam A，一种从 Piper betle Linn 中分离出来的马兜铃内酰胺。对雌激素和孕激素受体的结合亲和力分别为 -8.9 和 -9.0Kcal/mol（抑制常数 Ki=0.294muM 和 0.249muM），甚至大于报道的拮抗剂如 Rohitukine 和 OrgC（结合亲和力 -8.7 和 - 8.4Kcal/mol；Ki 分别为 0.443muM 和 0.685muM）。结合位点探索显示哌内酰胺 A (His 524, Leu 346, Thr 347) 比 Rohitukine 和 OrgC (Leu 718) 具有相关受体，分子动力学模拟进一步证实了这一点。该化合物的成药性符合利平斯基五法则，降低了心脏毒性、肝毒性、致突变性和生态毒性等毒性。内分泌干​​扰组和后来的对接引导分子模拟表明，哌内酰胺 A 具有较弱的结合亲和力和/或与核受体，尤其是 hERG 和细胞色素 P450 结合的可能性较低。高 Caco-2 渗透性表明更高的生物利用度，因此药物的治疗功效更高。肝毒性、致突变性和生态毒性。内分泌干​​扰组和后来的对接引导分子模拟表明，哌内酰胺 A 具有较弱的结合亲和力和/或与核受体，尤其是 hERG 和细胞色素 P450 结合的可能性较低。高 Caco-2 渗透性表明更高的生物利用度，因此药物的治疗功效更高。肝毒性、致突变性和生态毒性。内分泌干​​扰组和后来的对接引导分子模拟表明，哌内酰胺 A 具有较弱的结合亲和力和/或与核受体，尤其是 hERG 和细胞色素 P450 结合的可能性较低。高 Caco-2 渗透性表明更高的生物利用度，因此药物的治疗功效更高。