Israeli air strikes in the heart of Gaza City have flattened three buildings and killed at least 42 people, making it the deadliest single attack since heavy fighting broke out between Israel and the territory's militant Hamas rulers nearly a week ago.

The Gaza health ministry said 12 women and eight children were among those killed in Sunday's attack, with another 50 people injured.

Rescuers raced to pull survivors and bodies from the rubble following the assault.

Earlier, Israel said it had bombed the home of Gaza's top Hamas leader in a separate strike. It was the third such air attack targeting the homes of Hamas leaders in the last two days.

Israel appears to have stepped up its air strikes in recent days to inflict as much damage as possible on Hamas, as efforts to broker a ceasefire accelerate with the arrival of a US diplomat in the region and talks at the UN Security Council.

The military said it struck the homes of Yehiyeh Sinwar, the most senior Hamas leader inside the territory, and his brother Muhammad, another senior Hamas member. On Saturday it destroyed the home of Khalil al-Hayeh, a senior figure in Hamas's political branch.

Brigadier general Hidai Zilberman confirmed the strike on Sinwar's house in the southern Gaza town of Khan Younis to army radio. He said the home of his brother, who is in charge of Hamas "logistics and personnel", was also destroyed.

Hamas's upper echelon has gone into hiding in Gaza, and it is unlikely any were at home at the time of the strikes. Its top leader, Ismail Haniyeh, divides his time between Turkey and Qatar, both of which provide political support to the group.

Hamas and the Islamic Jihad militant group have acknowledged 20 fighters have been killed since the fighting broke out last Monday, while Israel says the real number is far higher.

At least 188 Palestinians have been killed in Gaza, including 55 children and 33 women, with more than 1,230 injured. Eight Israelis have been killed, including a five-year-old boy and a soldier.

Hamas and other militant groups have fired some 2,900 rockets into Israel since Monday, when tensions over a holy site in Jerusalem and the threatened eviction of dozens of Palestinian families from a nearby neighbourhood boiled over.

Israel has carried out hundreds of air strikes across the impoverished and blockaded territory, which is home to more than two million Palestinians, and brought down a number of high-rise buildings - including one that housed The Associated Press office in Gaza.

International human rights group Amnesty International has called on the International Criminal Court to investigate the Israeli attack on the building housing media organisations and Sunday's air strikes, calling incidents such as these war crimes.

Meanwhile, the Biden administration in the US has affirmed its support for Israel while working to de-escalate the crisis.

US diplomat Hady Amr met with Israeli defence minister Benny Gantz, who thanked America for its support.

Mr Gantz said Israel "takes every precaution to strike at military targets only and avoid harming civilians, while its civilians are the targets of indiscriminate attack".

Elsewhere, the United Nations chief appealed to Israelis and Palestinians in Gaza to immediately stop the "utterly appalling" escalation in fighting and "senseless cycle of bloodshed, terror and destruction" at the start of a high-level emergency meeting of the UN Security Council.

Secretary-General Antonio Guterres told the virtual meeting on Sunday that "the United Nations is actively engaging all sides towards an immediate ceasefire".